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

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.