CAR T-Cell Immunotherapy Treating T-ALL: Challenges and Opportunities

T-cell acute lymphoblastic leukemia (T-ALL), a form of T-cell malignancy, is a typically aggressive hematological malignancy with high rates of disease relapse and a poor prognosis. Current guidelines do not recommend any specific treatments for these patients, and only allogeneic stem cell transplant, which is associated with potential risks and toxicities, is a curative therapy. Recent clinical trials showed that immunotherapies, including monoclonal antibodies, checkpoint inhibitors, and CAR T therapies, are successful in treating hematologic malignancies. CAR T cells, which specifically target the B-cell surface antigen CD19, have demonstrated remarkable efficacy in the treatment of B-cell acute leukemia, and some progress has been made in the treatment of other hematologic malignancies. However, the development of CAR T-cell immunotherapy targeting T-cell malignancies appears more challenging due to the potential risks of fratricide, T-cell aplasia, immunosuppression, and product contamination. In this review, we discuss the current status of and challenges related to CAR T-cell immunotherapy for T-ALL and review potential strategies to overcome these limitations.

Automated summary

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with high relapse rates and poor prognosis. Current guidelines do not recommend specific treatments, and allogeneic stem cell transplant is the only curative therapy with potential risks. Recent trials have shown success in treating hematologic malignancies with immunotherapies such as monoclonal antibodies, checkpoint inhibitors, and CAR T therapies. However, developing CAR T immunotherapy for T-ALL is challenging due to potential risks of fratricide, T-cell aplasia, immunosuppression, and product contamination.