Clinical implications for CAR T cell persistence and functional phenotype in patients treated with CD19 CAR T cell therapy.

Abstract

Abstract Understanding the critical relationship between cancer and the immune system has led to novel immune therapies including chimeric antigen receptor (CAR) T-cell therapy. In the clinic, CAR T cells have been most effective against hematological malignancies. CD19 is expressed in almost all stages of B cell development as well as in most B cell malignancies, making it an ideal antigen to target using CAR T cells. Despite the promising efficacy of CD19 CAR T cell therapy, there remains a subset of patients who are resistant to therapy. At Loyola University Chicago, we initiated a CD19 CAR T cell clinical trial in 2020. A total of 6 patients were treated on protocol, with a 50% durable complete response rate. Importantly, no treated patients experienced severe side effects. Unique to the CD19 CAR T cells, is the incorporation of a CD34 marker gene (CD34t) in the CAR retroviral construct used for T cell transduction. The use of CD34t allows us to track infused CAR T cells in the blood. With the ability to distinguish CD19 CAR T cells from the endogenous T cell population, we have developed an immunofluorescence staining panel of 39 functional cell surface proteins to study the treated patient blood samples. We found that CD19 CAR T cells persist regardless of clinical outcome. We are studying the changing CAR T cell phenotype in patients with varying clinical outcomes to identify phenotypic trends that may have clinical implications and could serve as relevant clinical biomarkers.