Foundational Principles for the Quantitative Translation of T‐Cell Therapeutics for Hematologic Malignancies and Immunology

T-cell engaging antibodies (TCEs) and chimeric antigen receptor (CAR) T cells (CAR-T cells) are among precision medicine therapies that have revolutionized the treatment of hematologic cancers. Their success in oncology has piqued interest in translating this promise into additional indications, such as autoimmune disorders. This review discusses the foundational principles for mechanistic modeling to provide a unified assessment framework for cross-modality (i.e., CAR-T cells vs. TCEs) and cross-indication (i.e., oncology vs. immunology) translation. This framework captures the unique elements of each modality, such as CAR-T cellular kinetics, TCE pharmacokinetics, and complex formation with target cells, as well as shared elements such as B-cell kinetics and biodistribution across indications. We describe how this integrated approach can lead to informed decision making for more personalized and effective treatment strategies with these immune therapies.

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Publication Details

Journal
Clinical Pharmacology & Therapeutics
Published
2025-10-02
DOI
https://doi.org/10.1002/cpt.70077
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
0.00
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article

Foundational Principles for the Quantitative Translation of T‐Cell Therapeutics for Hematologic Malignancies and Immunology

Jan‐Frederik Schlender, Arthur J. Van De Vyver, Peter Ashcroft, Eshita Khera et al.
Clinical Pharmacology & Therapeutics
CAR-T cell therapy research
article

Foundational Principles for the Quantitative Translation of T‐Cell Therapeutics for Hematologic Malignancies and Immunology

Jan‐Frederik Schlender, Arthur J. Van De Vyver, Peter Ashcroft, Eshita Khera, Sarah McFann, Suzanne Gaudet, A Ferguson
article en

Abstract

T-cell engaging antibodies (TCEs) and chimeric antigen receptor (CAR) T cells (CAR-T cells) are among precision medicine therapies that have revolutionized the treatment of hematologic cancers. Their success in oncology has piqued interest in translating this promise into additional indications, such as autoimmune disorders. This review discusses the foundational principles for mechanistic modeling to provide a unified assessment framework for cross-modality (i.e., CAR-T cells vs. TCEs) and cross-indication (i.e., oncology vs. immunology) translation. This framework captures the unique elements of each modality, such as CAR-T cellular kinetics, TCE pharmacokinetics, and complex formation with target cells, as well as shared elements such as B-cell kinetics and biodistribution across indications. We describe how this integrated approach can lead to informed decision making for more personalized and effective treatment strategies with these immune therapies.

Clinical Pharmacology & TherapeuticsVol. 119(1)
Novartis (Switzerland) (CH), Health First (US), Novartis (United States) (US)
Openalex Percentile: Top 63%
CAR-T cell therapy research
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