Early Survival Prediction Framework in CD19-Specific CAR-T Cell Immunotherapy Using a Quantitative Systems Pharmacology Model.

ABSTRACT: Chimeric antigen receptor (CAR)-T cell therapy has revolutionized treatment of relapsed/refractory non-Hodgkin lymphoma (NHL). However, since 36-60% of patients relapse, early response prediction is crucial. We present a novel population quantitative systems pharmacology model, integrating literature knowledge on physiology, immunology, and adoptive cell therapy together with 133 CAR-T cell phenotype, 1943 cytokine, and 48 metabolic tumor measurements. The model well described post-infusion concentrations of four CAR-T cell phenotypes and CD19⁺ metabolic tumor volume over 3 months after CAR-T cell infusion. Leveraging the model, we identified a low expansion subpopulation with significantly lower CAR-T cell expansion capacities amongst 19 NHL patients. Together with two patient-

SUBMITTER: Mueller-Schoell A 

PROVIDER: S-EPMC8199881 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature