Strategies for clinical dose optimization of T cell-engaging therapies in oncology
Innovative approaches in the design of T cell-engaging (TCE) molecules are ushering in a new wave of promising immunotherapies for the treatment of cancer. Their mechanism of action, which generates an in trans interaction to create a synthetic immune synapse, leads to complex and interconnected rel...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2023.2181016 |
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| author | Kathryn Ball Simon J Dovedi Pavan Vajjah Alex Phipps |
| author_facet | Kathryn Ball Simon J Dovedi Pavan Vajjah Alex Phipps |
| author_sort | Kathryn Ball |
| collection | DOAJ |
| description | Innovative approaches in the design of T cell-engaging (TCE) molecules are ushering in a new wave of promising immunotherapies for the treatment of cancer. Their mechanism of action, which generates an in trans interaction to create a synthetic immune synapse, leads to complex and interconnected relationships between the exposure, efficacy, and toxicity of these drugs. Challenges thus arise when designing optimal clinical dose regimens for TCEs with narrow therapeutic windows, with a variety of dosing strategies being evaluated to mitigate key side effects such as cytokine release syndrome, neurotoxicity, and on-target off-tumor toxicities. This review evaluates the current approaches to dose optimization throughout the preclinical and clinical development of TCEs, along with perspectives for improvement of these strategies. Quantitative approaches used to aid the understanding of dose-exposure-response relationships are highlighted, along with opportunities to guide the rational design of next-generation TCE molecules, and optimize their dose regimens in patients. |
| format | Article |
| id | doaj-art-3e72b1cc99f146d7aaec4efa9cd6c54c |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-3e72b1cc99f146d7aaec4efa9cd6c54c2025-08-20T03:55:53ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2181016Strategies for clinical dose optimization of T cell-engaging therapies in oncologyKathryn Ball0Simon J Dovedi1Pavan Vajjah2Alex Phipps3Clinical Pharmacology and Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UKEarly Oncology R&D, AstraZeneca, Cambridge, UKClinical Pharmacology and Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UKClinical Pharmacology and Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UKInnovative approaches in the design of T cell-engaging (TCE) molecules are ushering in a new wave of promising immunotherapies for the treatment of cancer. Their mechanism of action, which generates an in trans interaction to create a synthetic immune synapse, leads to complex and interconnected relationships between the exposure, efficacy, and toxicity of these drugs. Challenges thus arise when designing optimal clinical dose regimens for TCEs with narrow therapeutic windows, with a variety of dosing strategies being evaluated to mitigate key side effects such as cytokine release syndrome, neurotoxicity, and on-target off-tumor toxicities. This review evaluates the current approaches to dose optimization throughout the preclinical and clinical development of TCEs, along with perspectives for improvement of these strategies. Quantitative approaches used to aid the understanding of dose-exposure-response relationships are highlighted, along with opportunities to guide the rational design of next-generation TCE molecules, and optimize their dose regimens in patients.https://www.tandfonline.com/doi/10.1080/19420862.2023.2181016T-cell engagerimmune oncologybispecific antibodydose optimizationquantitative clinical pharmacologytranslational PK/PD modeling |
| spellingShingle | Kathryn Ball Simon J Dovedi Pavan Vajjah Alex Phipps Strategies for clinical dose optimization of T cell-engaging therapies in oncology mAbs T-cell engager immune oncology bispecific antibody dose optimization quantitative clinical pharmacology translational PK/PD modeling |
| title | Strategies for clinical dose optimization of T cell-engaging therapies in oncology |
| title_full | Strategies for clinical dose optimization of T cell-engaging therapies in oncology |
| title_fullStr | Strategies for clinical dose optimization of T cell-engaging therapies in oncology |
| title_full_unstemmed | Strategies for clinical dose optimization of T cell-engaging therapies in oncology |
| title_short | Strategies for clinical dose optimization of T cell-engaging therapies in oncology |
| title_sort | strategies for clinical dose optimization of t cell engaging therapies in oncology |
| topic | T-cell engager immune oncology bispecific antibody dose optimization quantitative clinical pharmacology translational PK/PD modeling |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2023.2181016 |
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