The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review
‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may st...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Mazzarella, Luca [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2019transfer abstract |
|---|
| Schlagwörter: |
Colony stimulating factor-1 (CSF-1) pathway |
|---|
| Umfang: |
18 |
|---|
| Übergeordnetes Werk: |
Enthalten in: The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study - Hamzah, N. ELSEVIER, 2018, Amsterdam [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:117 ; year:2019 ; pages:14-31 ; extent:18 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.ejca.2019.04.035 |
|---|
| Katalog-ID: |
ELV047347244 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | ELV047347244 | ||
| 003 | DE-627 | ||
| 005 | 20230626015507.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 191021s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejca.2019.04.035 |2 doi | |
| 028 | 5 | 2 | |a GBV00000000000727.pica |
| 035 | |a (DE-627)ELV047347244 | ||
| 035 | |a (ELSEVIER)S0959-8049(19)30294-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q VZ |
| 084 | |a 44.52 |2 bkl | ||
| 100 | 1 | |a Mazzarella, Luca |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review |
| 264 | 1 | |c 2019transfer abstract | |
| 300 | |a 18 | ||
| 336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
| 337 | |a nicht spezifiziert |b z |2 rdamedia | ||
| 338 | |a nicht spezifiziert |b zu |2 rdacarrier | ||
| 520 | |a ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation | ||
| 520 | |a ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation | ||
| 650 | 7 | |a GITR |2 Elsevier | |
| 650 | 7 | |a LAG3 |2 Elsevier | |
| 650 | 7 | |a TLR, RLR and cGAS/STING |2 Elsevier | |
| 650 | 7 | |a Colony stimulating factor-1 (CSF-1) pathway |2 Elsevier | |
| 650 | 7 | |a Next generation immune-checkpoints |2 Elsevier | |
| 650 | 7 | |a 4-1BB |2 Elsevier | |
| 650 | 7 | |a TIGIT |2 Elsevier | |
| 650 | 7 | |a TIM3 |2 Elsevier | |
| 650 | 7 | |a IDO1 |2 Elsevier | |
| 700 | 1 | |a Duso, Bruno Achutti |4 oth | |
| 700 | 1 | |a Trapani, Dario |4 oth | |
| 700 | 1 | |a Belli, Carmen |4 oth | |
| 700 | 1 | |a D'Amico, Paolo |4 oth | |
| 700 | 1 | |a Ferraro, Emanuela |4 oth | |
| 700 | 1 | |a Viale, Giulia |4 oth | |
| 700 | 1 | |a Curigliano, Giuseppe |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a Hamzah, N. ELSEVIER |t The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study |d 2018 |g Amsterdam [u.a.] |w (DE-627)ELV000241849 |
| 773 | 1 | 8 | |g volume:117 |g year:2019 |g pages:14-31 |g extent:18 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.ejca.2019.04.035 |3 Volltext |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a GBV_ELV | ||
| 912 | |a SYSFLAG_U | ||
| 936 | b | k | |a 44.52 |j Therapie |x Medizin |q VZ |
| 951 | |a AR | ||
| 952 | |d 117 |j 2019 |h 14-31 |g 18 | ||
| author_variant |
l m lm |
|---|---|
| matchkey_str |
mazzarellalucadusobrunoachuttitrapanidar:2019----:heovnlnsaefeteeainmuehcpi |
| hierarchy_sort_str |
2019transfer abstract |
| bklnumber |
44.52 |
| publishDate |
2019 |
| allfields |
10.1016/j.ejca.2019.04.035 doi GBV00000000000727.pica (DE-627)ELV047347244 (ELSEVIER)S0959-8049(19)30294-1 DE-627 ger DE-627 rakwb eng 610 VZ 44.52 bkl Mazzarella, Luca verfasserin aut The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review 2019transfer abstract 18 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 Elsevier Duso, Bruno Achutti oth Trapani, Dario oth Belli, Carmen oth D'Amico, Paolo oth Ferraro, Emanuela oth Viale, Giulia oth Curigliano, Giuseppe oth Enthalten in Elsevier Hamzah, N. ELSEVIER The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study 2018 Amsterdam [u.a.] (DE-627)ELV000241849 volume:117 year:2019 pages:14-31 extent:18 https://doi.org/10.1016/j.ejca.2019.04.035 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 44.52 Therapie Medizin VZ AR 117 2019 14-31 18 |
| spelling |
10.1016/j.ejca.2019.04.035 doi GBV00000000000727.pica (DE-627)ELV047347244 (ELSEVIER)S0959-8049(19)30294-1 DE-627 ger DE-627 rakwb eng 610 VZ 44.52 bkl Mazzarella, Luca verfasserin aut The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review 2019transfer abstract 18 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 Elsevier Duso, Bruno Achutti oth Trapani, Dario oth Belli, Carmen oth D'Amico, Paolo oth Ferraro, Emanuela oth Viale, Giulia oth Curigliano, Giuseppe oth Enthalten in Elsevier Hamzah, N. ELSEVIER The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study 2018 Amsterdam [u.a.] (DE-627)ELV000241849 volume:117 year:2019 pages:14-31 extent:18 https://doi.org/10.1016/j.ejca.2019.04.035 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 44.52 Therapie Medizin VZ AR 117 2019 14-31 18 |
| allfields_unstemmed |
10.1016/j.ejca.2019.04.035 doi GBV00000000000727.pica (DE-627)ELV047347244 (ELSEVIER)S0959-8049(19)30294-1 DE-627 ger DE-627 rakwb eng 610 VZ 44.52 bkl Mazzarella, Luca verfasserin aut The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review 2019transfer abstract 18 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 Elsevier Duso, Bruno Achutti oth Trapani, Dario oth Belli, Carmen oth D'Amico, Paolo oth Ferraro, Emanuela oth Viale, Giulia oth Curigliano, Giuseppe oth Enthalten in Elsevier Hamzah, N. ELSEVIER The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study 2018 Amsterdam [u.a.] (DE-627)ELV000241849 volume:117 year:2019 pages:14-31 extent:18 https://doi.org/10.1016/j.ejca.2019.04.035 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 44.52 Therapie Medizin VZ AR 117 2019 14-31 18 |
| allfieldsGer |
10.1016/j.ejca.2019.04.035 doi GBV00000000000727.pica (DE-627)ELV047347244 (ELSEVIER)S0959-8049(19)30294-1 DE-627 ger DE-627 rakwb eng 610 VZ 44.52 bkl Mazzarella, Luca verfasserin aut The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review 2019transfer abstract 18 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 Elsevier Duso, Bruno Achutti oth Trapani, Dario oth Belli, Carmen oth D'Amico, Paolo oth Ferraro, Emanuela oth Viale, Giulia oth Curigliano, Giuseppe oth Enthalten in Elsevier Hamzah, N. ELSEVIER The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study 2018 Amsterdam [u.a.] (DE-627)ELV000241849 volume:117 year:2019 pages:14-31 extent:18 https://doi.org/10.1016/j.ejca.2019.04.035 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 44.52 Therapie Medizin VZ AR 117 2019 14-31 18 |
| allfieldsSound |
10.1016/j.ejca.2019.04.035 doi GBV00000000000727.pica (DE-627)ELV047347244 (ELSEVIER)S0959-8049(19)30294-1 DE-627 ger DE-627 rakwb eng 610 VZ 44.52 bkl Mazzarella, Luca verfasserin aut The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review 2019transfer abstract 18 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation ‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 Elsevier Duso, Bruno Achutti oth Trapani, Dario oth Belli, Carmen oth D'Amico, Paolo oth Ferraro, Emanuela oth Viale, Giulia oth Curigliano, Giuseppe oth Enthalten in Elsevier Hamzah, N. ELSEVIER The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study 2018 Amsterdam [u.a.] (DE-627)ELV000241849 volume:117 year:2019 pages:14-31 extent:18 https://doi.org/10.1016/j.ejca.2019.04.035 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 44.52 Therapie Medizin VZ AR 117 2019 14-31 18 |
| language |
English |
| source |
Enthalten in The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study Amsterdam [u.a.] volume:117 year:2019 pages:14-31 extent:18 |
| sourceStr |
Enthalten in The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study Amsterdam [u.a.] volume:117 year:2019 pages:14-31 extent:18 |
| format_phy_str_mv |
Article |
| bklname |
Therapie |
| institution |
findex.gbv.de |
| topic_facet |
GITR LAG3 TLR, RLR and cGAS/STING Colony stimulating factor-1 (CSF-1) pathway Next generation immune-checkpoints 4-1BB TIGIT TIM3 IDO1 |
| dewey-raw |
610 |
| isfreeaccess_bool |
false |
| container_title |
The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study |
| authorswithroles_txt_mv |
Mazzarella, Luca @@aut@@ Duso, Bruno Achutti @@oth@@ Trapani, Dario @@oth@@ Belli, Carmen @@oth@@ D'Amico, Paolo @@oth@@ Ferraro, Emanuela @@oth@@ Viale, Giulia @@oth@@ Curigliano, Giuseppe @@oth@@ |
| publishDateDaySort_date |
2019-01-01T00:00:00Z |
| hierarchy_top_id |
ELV000241849 |
| dewey-sort |
3610 |
| id |
ELV047347244 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV047347244</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230626015507.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">191021s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ejca.2019.04.035</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBV00000000000727.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV047347244</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0959-8049(19)30294-1</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.52</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Mazzarella, Luca</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="4"><subfield code="a">The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">18</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">GITR</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">LAG3</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">TLR, RLR and cGAS/STING</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Colony stimulating factor-1 (CSF-1) pathway</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Next generation immune-checkpoints</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">4-1BB</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">TIGIT</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">TIM3</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">IDO1</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Duso, Bruno Achutti</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Trapani, Dario</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Belli, Carmen</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">D'Amico, Paolo</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ferraro, Emanuela</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Viale, Giulia</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Curigliano, Giuseppe</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Hamzah, N. ELSEVIER</subfield><subfield code="t">The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study</subfield><subfield code="d">2018</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV000241849</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:117</subfield><subfield code="g">year:2019</subfield><subfield code="g">pages:14-31</subfield><subfield code="g">extent:18</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ejca.2019.04.035</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.52</subfield><subfield code="j">Therapie</subfield><subfield code="x">Medizin</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">117</subfield><subfield code="j">2019</subfield><subfield code="h">14-31</subfield><subfield code="g">18</subfield></datafield></record></collection>
|
| author |
Mazzarella, Luca |
| spellingShingle |
Mazzarella, Luca ddc 610 bkl 44.52 Elsevier GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review |
| authorStr |
Mazzarella, Luca |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)ELV000241849 |
| format |
electronic Article |
| dewey-ones |
610 - Medicine & health |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
elsevier |
| remote_str |
true |
| illustrated |
Not Illustrated |
| topic_title |
610 VZ 44.52 bkl The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 Elsevier |
| topic |
ddc 610 bkl 44.52 Elsevier GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 |
| topic_unstemmed |
ddc 610 bkl 44.52 Elsevier GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 |
| topic_browse |
ddc 610 bkl 44.52 Elsevier GITR Elsevier LAG3 Elsevier TLR, RLR and cGAS/STING Elsevier Colony stimulating factor-1 (CSF-1) pathway Elsevier Next generation immune-checkpoints Elsevier 4-1BB Elsevier TIGIT Elsevier TIM3 Elsevier IDO1 |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
b a d ba bad d t dt c b cb p d pd e f ef g v gv g c gc |
| hierarchy_parent_title |
The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study |
| hierarchy_parent_id |
ELV000241849 |
| dewey-tens |
610 - Medicine & health |
| hierarchy_top_title |
The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)ELV000241849 |
| title |
The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review |
| ctrlnum |
(DE-627)ELV047347244 (ELSEVIER)S0959-8049(19)30294-1 |
| title_full |
The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review |
| author_sort |
Mazzarella, Luca |
| journal |
The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study |
| journalStr |
The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
600 - Technology |
| recordtype |
marc |
| publishDateSort |
2019 |
| contenttype_str_mv |
zzz |
| container_start_page |
14 |
| author_browse |
Mazzarella, Luca |
| container_volume |
117 |
| physical |
18 |
| class |
610 VZ 44.52 bkl |
| format_se |
Elektronische Aufsätze |
| author-letter |
Mazzarella, Luca |
| doi_str_mv |
10.1016/j.ejca.2019.04.035 |
| dewey-full |
610 |
| title_sort |
evolving landscape of ‘next-generation’ immune checkpoint inhibitors: a review |
| title_auth |
The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review |
| abstract |
‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation |
| abstractGer |
‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation |
| abstract_unstemmed |
‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation |
| collection_details |
GBV_USEFLAG_U GBV_ELV SYSFLAG_U |
| title_short |
The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review |
| url |
https://doi.org/10.1016/j.ejca.2019.04.035 |
| remote_bool |
true |
| author2 |
Duso, Bruno Achutti Trapani, Dario Belli, Carmen D'Amico, Paolo Ferraro, Emanuela Viale, Giulia Curigliano, Giuseppe |
| author2Str |
Duso, Bruno Achutti Trapani, Dario Belli, Carmen D'Amico, Paolo Ferraro, Emanuela Viale, Giulia Curigliano, Giuseppe |
| ppnlink |
ELV000241849 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth oth oth oth |
| doi_str |
10.1016/j.ejca.2019.04.035 |
| up_date |
2024-07-06T22:39:00.819Z |
| _version_ |
1803871102771920896 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV047347244</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230626015507.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">191021s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ejca.2019.04.035</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBV00000000000727.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV047347244</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0959-8049(19)30294-1</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.52</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Mazzarella, Luca</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="4"><subfield code="a">The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">18</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">‘First-generation’ immune checkpoint inhibitors targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed death-ligand 1 (PD(L)1) have undoubtedly revolutionised the treatment of multiple cancers in the advanced setting. Targeting signalling pathways other than core inhibitory modules may strongly impact the outcome of the antitumour immune response. Drugs targeting these pathways (‘next-generation’ immune modulators, NGIMs) constitute a major frontier in translational research and have generated unprecedented scientific and financial investment. Here, we systematically reviewed published literature, abstracts from major cancer conferences and pharma pipelines to identify NGIMs that have reached clinical development. We identified 107 molecules targeting 16 pathways, which we classified into 6 groups according to function (inhibitory vs stimulatory) and cell of predominant expression (lymphoid, non-lymphoid and natural killer). We identified all registered past and ongoing clinical trials (n = 428). We summarise the preclinical rationale for these targets, extracting translationally relevant information, and review published and preliminary clinical results. Some targets like indoleamine-2,3-dioxygenase 1, lymphocyte activation gene-3 and IL15 have experienced exceptional growth of interest, measured in terms of activated studies and expected patient enrolment over time. We conclude that in this vast and rapidly changing drug development landscape, novel trial designs and better biomarker identification are necessary to optimise resource allocation</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">GITR</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">LAG3</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">TLR, RLR and cGAS/STING</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Colony stimulating factor-1 (CSF-1) pathway</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Next generation immune-checkpoints</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">4-1BB</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">TIGIT</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">TIM3</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">IDO1</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Duso, Bruno Achutti</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Trapani, Dario</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Belli, Carmen</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">D'Amico, Paolo</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ferraro, Emanuela</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Viale, Giulia</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Curigliano, Giuseppe</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Hamzah, N. ELSEVIER</subfield><subfield code="t">The effect of early cognitive therapy in improving cognitive functions using neuropsychology and diffusion tensor imaging measurements following mild traumatic brain injury: A pilot study</subfield><subfield code="d">2018</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV000241849</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:117</subfield><subfield code="g">year:2019</subfield><subfield code="g">pages:14-31</subfield><subfield code="g">extent:18</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ejca.2019.04.035</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.52</subfield><subfield code="j">Therapie</subfield><subfield code="x">Medizin</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">117</subfield><subfield code="j">2019</subfield><subfield code="h">14-31</subfield><subfield code="g">18</subfield></datafield></record></collection>
|
| score |
7.400769 |