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What is it about?

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell lymphoid neoplasia and, in some instances, improved disease outcomes. Resistant diseases have been treated with success with CAR T-cells. These therapeutic successes have triggered the application of CAR-T cell therapy to other hematologic tumors, including T-cell malignancies.

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Why is it important?

However, the success of CAR-T cell therapies in T-cell neoplasms was considerably more limited due to the existence of some limiting factors. Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of B-cell lymphoid neoplasia and, in some cases, has significantly improved disease outcomes. Resistant diseases have also been successfully treated with CAR-T cells. This success has led to the exploration of CAR-T cell therapy for other hematologic tumors, including T-cell malignancies. However, the effectiveness of CAR-T cell therapies in treating T-cell neoplasms has been notably limited due to several constraints.Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of B-cell lymphoid neoplasia and, in some cases, has significantly improved disease outcomes. Resistant diseases have also seen successful treatment with CAR-T cells. This success has led to the exploration of CAR-T cell therapy for other hematologic tumors, including T-cell malignancies. However, the effectiveness of CAR-T cell therapies in treating T-cell neoplasms has been notably limited due to several constraints.Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of B-cell lymphoid neoplasia and, in some cases, has significantly improved disease outcomes. Resistant diseases have also seen successful treatment with CAR-T cells. This success has led to the exploration of CAR-T cell therapy for other hematologic tumors, including T-cell malignancies. However, the effectiveness of CAR-T cell therapies in treating T-cell neoplasms has been notably limited due to several constraints.Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of B-cell lymphoid neoplasia and, in some cases, has significantly improved disease outcomes. Resistant diseases have also seen successful treatment with CAR-T cells. This success has led to the exploration of CAR-T cell therapy for other hematologic tumors, including T-cell malignancies. However, the effectiveness of CAR-T cell therapies in treating T-cell neoplasms has been notably limited due to several constraints.Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of B-cell lymphoid neoplasia and, in some cases, has significantly improved disease outcomes. Resistant diseases have also seen successful treatment with CAR-T cells. This success has led to the exploration of CAR-T cell therapy for other hematologic tumors, including T-cell malignancies. However, the effectiveness of CAR-T cell therapies in treating T-cell neoplasms has been notably limited due to several constraints.Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of B-cell lymphoid neoplasia and, in some cases, has significantly improved disease outcomes. Resistant diseases have also seen successful treatment with CAR-T cells. This success has led to the exploration of CAR-T cell therapy for other hematologic tumors, including T-cell malignancies. However, the effectiveness of CAR-T cell therapies in treating T-cell neoplasms has been notably limited due to several constraints. Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of B-cell lymphoid neoplasia and, in some cases, has significantly improved disease outcomes. Resistant diseases have also been successfully treated with CAR-T cells. This success has led to the exploration of CAR-T cell therapy for other hematologic tumors, including T-cell malignancies. However, the effectiveness of CAR-T cell therapies in treating T-cell neoplasms has been notably limited due to several constraints. Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of B-cell lymphoid neoplasia and, in some cases, has significantly improved disease outcomes. Resistant diseases have also been successfully treated with CAR-T cells. This success has led to the exploration of CAR-T cell therapy for other hematologic tumors, including T-cell malignancies. However, the effectiveness of CAR-T cell therapies in treating T-cell neoplasms has been notably limited due to several constraints.

Perspectives

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CAR-T cell therapy for T-cell malignancies is still in its infancy, and additional studies are required before its introduction in the standard treatment strategy for these diseases. Several factors have hampered the successful development of CAR-T cell technology in the therapy of T-cell malignancies: (i) tumor contamination, related to the admixture of manufactured CAR-T cell products with leukemic/lymphoma T-cells; (ii) T cell aplasia as a consequence of the unwanted targeting extended also to normal T cells; (iii) fratricide, a phenomenon related to the cytotoxicity exerted by CAR-T cells not only targeting malignant T cells but also other CAR-T cells expressing the target antigen. In spite of these limitations, only some studies based on enough patients with T-cell malignancies, with a follow-up of at least two years, have provided initial encouraging results that need to be confirmed in larger prospective studies. Future studies have to clarify: (i) the "optimal" membrane antigen to be targeted by CAR-T cells on the surface of malignant T-cells; (ii) the comparative evaluation of auto-and allo-CAR-T cells in terms of safety and efficacy; (iii) the role of CAR-T cell therapy alone or as a bridge to allo-HSCT.

Prof. Giuseppe Leone
Universita Cattolica del Sacro Cuore

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This page is a summary of: CAR-T CELL THERAPY FOR T-CELL MALIGNANCIES, Mediterranean Journal of Hematology and Infectious Diseases, February 2024, Institute of Hematology, Catholic University,
DOI: 10.4084/mjhid.2024.031.
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