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

• Type of Material: Article
• Authors: Lauren C. Fleischer, Emory University; H Trent Spencer, Emory University; Sunil Sudhir Raikar, Emory University
• Language: English
• Date: 2019-12-29
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13045-019-0801-y
• Title of Journal or Parent Work: Journal of Hematology and Oncology
• ISSN: 1756-8722
• Volume: 12
• Issue: 1
• Start Page: 141
• End Page: 141
• Grant/Funding Information: This work is supported by grants from the National Institutes of Health (F31CA221002, K12HD072245); Hyundai Hope of Wheels; Curing Kids Cancer; and Children’s Healthcare of Atlanta.
• Keywords: T-ALL; Immunotherapy; CAR; T cell lymphoma
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

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.