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
Autor*in: |
Mazzarella, Luca [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2019transfer abstract |
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Schlagwörter: |
Colony stimulating factor-1 (CSF-1) pathway |
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Umfang: |
18 |
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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.] |
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Übergeordnetes Werk: |
volume:117 ; year:2019 ; pages:14-31 ; extent:18 |
Links: |
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DOI / URN: |
10.1016/j.ejca.2019.04.035 |
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Katalog-ID: |
ELV047347244 |
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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 | ||
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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 |
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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 |
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evolving landscape of ‘next-generation’ immune checkpoint inhibitors: a review |
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The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review |
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‘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 |
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The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: A review |
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