A narrative review of critical factors for better efficacy of CD19 chimeric antigen receptor T cell therapy in the treatment of B cell malignancies

Abstract

B cell malignancies are classified as different types such as B cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL) and B cell non-Hodgkin lymphoma (NHL) based on cell surface expression of various clusters of differentiation molecules. CD19 is a B cell lineage-specific antigen which is expressed on malignant B cells in patients with B-ALL, CLL and NHL. Adoptive transfer of T cells that are genetically modified to express a CD19-specific chimeric antigen receptor (CAR) represents a promising clinical strategy for patients with B cell malignancies. CD19-CAR T cell therapy has achieved high response rates and durable remissions on B cell malignancies. However, the efficacy of CAR-T therapy is still inefficient and the critical factors for better efficacy remain unclear. In this review, we summarized the critical factors for better efficacy of CD19 CAR-T cells in B-lineage malignancies including B-ALL, B-CLL and lymphoma. T cell persistence, lymphodepletion regimen, CD3/CD28 beads treatment and no IL-2 administration to T cells were positively associated with better responses. The method of enhancing the persistence of CAR-T cells need to be further optimized in order to improve the clinical efficacy in the treatment of B cell malignancies. In order to improve the therapeutic effect of CAR-T therapy, new therapeutic strategies should be developed to make factors which influence efficacy the more beneficial.