How to train your T cell: genetically engineered chimeric antigen receptor T cells versus bispecific T-cell engagers to target CD19 in B acute lymphoblastic leukemia

Abstract

Antigen-specific T cell–based immunotherapy is getting its day in the sun. The contemporaneous development of two potent CD19-specific immunotherapeutic modalities for the treatment of B-cell malignancies provides exciting opportunities for patients, physicians and scientists alike. Patients with relapsed, refractory or poor-risk B-cell acute lymphoblastic leukemia (ALL) previously had few therapeutic options and now have two potential new lifelines. Physicians will have the choice between two powerful modalities and indeed could potentially enroll some patients on trials exploring both modalities if needed. For scientists interested in tumor immunology, the advent of chimeric antigen receptor T-cell therapy and of bispecific T-cell engagers (BiTEs) provides unprecedented opportunities to explore the promise and limitations of antigen-specific T-cell therapy in the context of human leukemia. In this article, we compare chimeric antigen receptor T cells and BiTEs targeting CD19 in B-cell ALL in the setting of the available clinical literature.

Keywords:

• adoptive cell therapy
• acute lymphoblastic leukemia
• B-cell acute lymphoblastic leukemia
• bispecific T-cell engager
• blinatumomab
• CART19
• CD19
• chimeric antigen receptor
• CTL019
• immunotherapy
• lymphoma
• non-Hodgkin lymphoma

Declaration of interest

M Ruella and S Gill receive research funding from Novartis. M Ruella is partly supported by the EMD-Serono Clinical Immunotherapy Fellowship from the Society for Immunotherapy of Cancer (SITC). M Ruella has a research grant from the Gabrielle Angel’s Foundation. S Gill career development grant from the American Society of Hematology, and research funding from the Leukemia & Lymphoma Society. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.