Old and new targets for immunotherapy of B cell acute lymphoblastic leukemia

Abstract

B cell-specific antigens such as CD20 and CD19 are the leading examples of clinically utilized targets for cancer immunotherapy. Rituximab, the anti-CD20 monoclonal antibody (mAb) approved for the treatment of B cell lymphoma in 1997, was the earliest mAb drug ever registered in cancer immunotherapy. The clinical success of chimeric antigen receptor (CAR)-modified T cells has been demonstrated in patients with B cell acute lymphoblastic leukemia (B-ALL), and CD19-directed CAR-T cells were the first CAR therapy ever approved to treat cancer patients. While surface antigen-targeting immunotherapies play a significant role in the therapy of B-ALL, in particular in the treatment of relapsed and refractory patients, they have some limitations and face continuous challenges. Herein, I review the types of antigen-specific immunotherapies that are used in the treatment of B-ALL, including naked mAbs, antibody-drug conjugates, B cell-specific T cell engagers, and CAR-modified T cells. I discuss the requirements for good immunotherapy targets and summarize the main methods used to identify novel putative targets. I present an overview of B cell-specific and non-B cell-specific target antigens, both already used in clinics and tested in preclinical models. I also discuss limitations of current B-ALL immunotherapy, attempts to overcome these limitations, and future directions of immunotherapy research.