Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions

• Main Authors: Lauren C. Fleischer, H. Trent Spencer, Sunil S. Raikar
• Format: Article
• Language: English
• Published: BMC 2019-12-01
• Series: Journal of Hematology & Oncology
• Subjects: CAR; Immunotherapy; T-ALL; T cell lymphoma
• Online Access: https://doi.org/10.1186/s13045-019-0801-y

Abstract Chimeric antigen receptor (CAR) T cell therapy has been successful in treating B cell malignancies in clinical trials; however, fewer studies have evaluated CAR T cell therapy for the treatment of T cell malignancies. There are many challenges in translating this therapy for T cell disease, including fratricide, T cell aplasia, and product contamination. To the best of our knowledge, no tumor-specific antigen has been identified with universal expression on cancerous T cells, hindering CAR T cell therapy for these malignancies. Numerous approaches have been assessed to address each of these challenges, such as (i) disrupting target antigen expression on CAR-modified T cells, (ii) targeting antigens with limited expression on T cells, and (iii) using third party donor cells that are either non-alloreactive or have been genome edited at the T cell receptor α constant (TRAC) locus. In this review, we discuss CAR approaches that have been explored both in preclinical and clinical studies targeting T cell antigens, as well as examine other potential strategies that can be used to successfully translate this therapy for T cell disease.