Critical testing and parameters for consideration when manufacturing and evaluating tumor–associated antigen-specific T cells

Abstract The past year has seen remarkable translation of cellular and gene therapies, with U.S. Food and Drug Administration (FDA) approval of three chimeric antigen receptor (CAR) T-cell products, multiple gene therapy products, and the initiation of countless other pivotal clinical trials. What makes these new drugs most remarkable is their path to commercialization: they have unique requirements compared with traditional pharmaceutical drugs and require different potency assays, critical quality attributes and parameters, pharmacological and toxicological data, and in vivo efficacy testing. What's more, each biologic requires its own unique set of tests and parameters. Here we describe the unique tests associated with ex vivo –expanded tumor-associated antigen T cells (TAA-T). These tests include functional assays to determine potency, specificity, and identity; tests for pathogenic contaminants, such as bacteria and fungus as well as other contaminants such as Mycoplasma and endotoxin; tests for product characterization, tests to evaluate T-cell persistence and product efficacy; and finally, recommendations for critical quality attributes and parameters associated with the expansion of TAA-Ts.