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

Journal of Hematology & Oncology

Sunil S. Raikar¹  H. Trent Spencer²  Lauren C. Fleischer² 

[1] Cell and Gene Therapy Program, Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University School of Medicine;Molecular and Systems Pharmacology Graduate Program, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University School of Medicine;

关键词: CAR;    Immunotherapy;    T-ALL;    T cell lymphoma;   

DOI  :  10.1186/s13045-019-0801-y

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown