Model-informed drug development of autologous CAR-T cell therapy: Strategies to optimize CAR-T cell exposure leveraging cell kinetic/dynamic modeling

Oncology

MIDD

CPT Pharmacometrics Syst Pharmacol. 2023 Nov;12(11):1577-1590

Mc Laughlin AM, Milligan PA, Yee C, Bergstrand M

Extensive literature review conducted by a collaborative team at Pharmetheus and the MD Anderson Cancer Center to identify actionable variables - design elements in CAR-T cell discovery, development, and clinical practice - that could be modified to optimize CAR-T cell exposure within a well-informed model-informed drug development (MIDD) program.

Autologous chimeric antigen receptor (CAR)-T cell therapy is a novel therapeutic modality, in which a patient's own immune cells are collected, genetically modified to target the patient's tumor cells, and then re-infused into the patient's body.

"This therapy has significantly transformed the treatment of aggressive hematological malignancies." explains Anna Mc Laughlin, "However, despite its success, up to 60% of patients do not respond long-term. Alternative approaches beyond dose titration are required to increase exposure"