Chimeric antigen receptor T cells march into T cell malignancies

Abstract

T cell malignancies represent a diverse collection of leukemia/lymphoma conditions in humans arising from aberrant T cells. Such malignancies are often associated with poor clinical prognoses, cancer relapse, as well as progressive resistance to anti-cancer treatments. While chimeric antigen receptor (CAR) T cell immunotherapy has emerged as a revolutionary treatment strategy that is highly effective for treating B cell malignancies, its application as a treatment for T cell malignancies remains to be better explored. Furthermore, the effectiveness of CAR-T treatment in T cell malignancies is significantly influenced by the quality of contamination-free CAR-T cells during the manufacturing process, as well as by multiple characteristics of such malignancies, including the sharing of antigens across normal and malignant T cells, fratricide, and T cell aplasia. In this review, we provide a detailed account of the current developments in the clinical application of CAR-T therapy to treat T cell malignancies, offer strategies for addressing current challenges, and outline a roadmap toward its effective implementation as a broad treatment option for this condition.

Keywords: CAR-T; CAR-T product contamination; Fratricide; T cell aplasia; T cell malignancies.

Fig. 1

Developmental overview of T lymphocytes. Hematopoietic stem cells in the bone marrow migrate to the thymus to differentiate into lymphoid precursor cells, which then undergo two key events, TCR gene rearrangement and thymic selection, to differentiate into many different types of T cells and then migrate into the peripheral blood circulation to carry out their immune functions

Fig. 2

The basic structure and evolution of CAR

Fig. 3

The challenges and solutions of CAR-T therapy for T cell malignancies

Fig. 4

Preliminary efficacy of CCL25-CAR-T targeting CCR9. CCL25, the natural ligand of CCR9, was used to prepare CAR-T cells targeting CCR9, which had the killing effect in T cell malignant tumor cell lines MOIT-4 and HUT78