biostudies-literatureFleischer LCCuring Kids CancerNICHD NIH HHSHyundai Hope On WheelsChildren's Healthcare of AtlantaNational Cancer InstituteNCI NIH HHSNIGMS NIH HHSNational Institute of Child Health and Human Development141https://www.ebi.ac.uk/biostudies/studies/S-EPMC6936092biostudies-literatureUnknown12(1)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.Journal of hematology & oncologyTargeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions.PMC6936092K12HD072245F31CA221002K12 HD072245Young Investigator GrantT32 GM008602Raikar SSSpencer HTFleischer LCfalseTargeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions.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.2019-01-01T00:00:00Z2019 Dec2025-04-04T10:43:20.192Z2020-05-22T01:35:17ZS-EPMC69360923188495510.1186/s13045-019-0801-y