Comparative Pre-Clinical Analysis of CD20-Specific CAR T Cells Encompassing 1F5-, Leu16-, and 2F2-Based Antigen-Recognition Moieties

Abstract

Over the past decade, CAR T cell therapy for patients with B cell malignancies has evolved from an experimental technique to a clinically feasible option. To date, four CAR T cell products specific for a B cell surface marker, CD19, have been approved by the FDA. Despite the spectacular rates of complete remission in r/r ALL and NHL patients, a significant proportion of patients still relapse, frequently with the CD19 low/negative tumor phenotype. To address this issue, additional B cell surface molecules such as CD20 were proposed as targets for CAR T cells. Here, we performed a side-by-side comparison of the activity of CD20-specific CAR T cells based on the antigen-recognition modules derived from the murine antibodies, 1F5 and Leu16, and from the human antibody, 2F2. Whereas CD20-specific CAR T cells differed from CD19-specific CAR T cells in terms of subpopulation composition and cytokine secretion, they displayed similar in vitro and in vivo potency.