Development of bispecific T cell engagers: harnessing quantitative systems pharmacology

Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limi...
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Gespeichert in:

Autor*in:	Qi, Timothy [verfasserIn] Liao, Xiaozhi [verfasserIn] Cao, Yanguang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	bispecific T cell engager cancer quantitative systems pharmacology

Übergeordnetes Werk:	Enthalten in: Trends in pharmacological sciences - Amsterdam [u.a.] : Elsevier Science, 1979, 44, Seite 880-890
Übergeordnetes Werk:	volume:44 ; pages:880-890

DOI / URN:	10.1016/j.tips.2023.09.009

Katalog-ID:	ELV065618785

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allfields	10.1016/j.tips.2023.09.009 doi (DE-627)ELV065618785 (ELSEVIER)S0165-6147(23)00211-0 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.38 bkl 44.40 bkl Qi, Timothy verfasserin aut Development of bispecific T cell engagers: harnessing quantitative systems pharmacology 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development. bispecific T cell engager cancer quantitative systems pharmacology Liao, Xiaozhi verfasserin aut Cao, Yanguang verfasserin (orcid)0000-0002-3974-9073 aut Enthalten in Trends in pharmacological sciences Amsterdam [u.a.] : Elsevier Science, 1979 44, Seite 880-890 Online-Ressource (DE-627)320490912 (DE-600)2011007-8 (DE-576)116726067 1873-3735 nnns volume:44 pages:880-890 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ 44.40 Pharmazie Pharmazeutika VZ AR 44 880-890
spelling	10.1016/j.tips.2023.09.009 doi (DE-627)ELV065618785 (ELSEVIER)S0165-6147(23)00211-0 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.38 bkl 44.40 bkl Qi, Timothy verfasserin aut Development of bispecific T cell engagers: harnessing quantitative systems pharmacology 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development. bispecific T cell engager cancer quantitative systems pharmacology Liao, Xiaozhi verfasserin aut Cao, Yanguang verfasserin (orcid)0000-0002-3974-9073 aut Enthalten in Trends in pharmacological sciences Amsterdam [u.a.] : Elsevier Science, 1979 44, Seite 880-890 Online-Ressource (DE-627)320490912 (DE-600)2011007-8 (DE-576)116726067 1873-3735 nnns volume:44 pages:880-890 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ 44.40 Pharmazie Pharmazeutika VZ AR 44 880-890
allfields_unstemmed	10.1016/j.tips.2023.09.009 doi (DE-627)ELV065618785 (ELSEVIER)S0165-6147(23)00211-0 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.38 bkl 44.40 bkl Qi, Timothy verfasserin aut Development of bispecific T cell engagers: harnessing quantitative systems pharmacology 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development. bispecific T cell engager cancer quantitative systems pharmacology Liao, Xiaozhi verfasserin aut Cao, Yanguang verfasserin (orcid)0000-0002-3974-9073 aut Enthalten in Trends in pharmacological sciences Amsterdam [u.a.] : Elsevier Science, 1979 44, Seite 880-890 Online-Ressource (DE-627)320490912 (DE-600)2011007-8 (DE-576)116726067 1873-3735 nnns volume:44 pages:880-890 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ 44.40 Pharmazie Pharmazeutika VZ AR 44 880-890
allfieldsGer	10.1016/j.tips.2023.09.009 doi (DE-627)ELV065618785 (ELSEVIER)S0165-6147(23)00211-0 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.38 bkl 44.40 bkl Qi, Timothy verfasserin aut Development of bispecific T cell engagers: harnessing quantitative systems pharmacology 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development. bispecific T cell engager cancer quantitative systems pharmacology Liao, Xiaozhi verfasserin aut Cao, Yanguang verfasserin (orcid)0000-0002-3974-9073 aut Enthalten in Trends in pharmacological sciences Amsterdam [u.a.] : Elsevier Science, 1979 44, Seite 880-890 Online-Ressource (DE-627)320490912 (DE-600)2011007-8 (DE-576)116726067 1873-3735 nnns volume:44 pages:880-890 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ 44.40 Pharmazie Pharmazeutika VZ AR 44 880-890
allfieldsSound	10.1016/j.tips.2023.09.009 doi (DE-627)ELV065618785 (ELSEVIER)S0165-6147(23)00211-0 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.38 bkl 44.40 bkl Qi, Timothy verfasserin aut Development of bispecific T cell engagers: harnessing quantitative systems pharmacology 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development. bispecific T cell engager cancer quantitative systems pharmacology Liao, Xiaozhi verfasserin aut Cao, Yanguang verfasserin (orcid)0000-0002-3974-9073 aut Enthalten in Trends in pharmacological sciences Amsterdam [u.a.] : Elsevier Science, 1979 44, Seite 880-890 Online-Ressource (DE-627)320490912 (DE-600)2011007-8 (DE-576)116726067 1873-3735 nnns volume:44 pages:880-890 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ 44.40 Pharmazie Pharmazeutika VZ AR 44 880-890
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author	Qi, Timothy
spellingShingle	Qi, Timothy ddc 610 ssgn 15,3 fid PHARM bkl 44.38 bkl 44.40 misc bispecific T cell engager misc cancer misc quantitative systems pharmacology Development of bispecific T cell engagers: harnessing quantitative systems pharmacology
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title	Development of bispecific T cell engagers: harnessing quantitative systems pharmacology
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title_full	Development of bispecific T cell engagers: harnessing quantitative systems pharmacology
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title_sort	development of bispecific t cell engagers: harnessing quantitative systems pharmacology
title_auth	Development of bispecific T cell engagers: harnessing quantitative systems pharmacology
abstract	Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development.
abstractGer	Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development.
abstract_unstemmed	Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development.
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title_short	Development of bispecific T cell engagers: harnessing quantitative systems pharmacology
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doi_str	10.1016/j.tips.2023.09.009
up_date	2024-07-06T23:39:38.650Z
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