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Review
. 2025 Feb 25;9(4):913-923.
doi: 10.1182/bloodadvances.2023012263.

CAR T-cell therapies for T-cell malignancies: does cellular immunotherapy represent the best chance of cure?

Nicola Maciocia  1 , Brandon Wade  1 , Paul Maciocia  1
Affiliations
Review

CAR T-cell therapies for T-cell malignancies: does cellular immunotherapy represent the best chance of cure?

Nicola Maciocia et al. Blood Adv. .

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has proven successful for B-cell lymphomas and leukemias. This success has inspired the development of CAR-T for T-cell malignancies. T-cell lymphomas and T-cell acute lymphoblastic leukemia (T-ALL) are highly heterogenous diseases but are united by poor prognosis in the relapsed/refractory setting and the lack of any novel, targeted therapies. CAR-T therapy is a promising solution for these diseases but carries a number of challenges, principally that target antigens are typically shared between malignant and normal T cells. This can cause issues with fratricide and T-cell aplasia. In this review we discuss the current state of CAR-T treatment for T-ALL and T-cell lymphomas, highlighting recent novel clinical data for T-cell malignancies and discuss lessons that can be learned for future research in this area.

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Conflict of interest statement

Conflict-of-interest disclosure: P.M. owns stock in a publicly traded company, Autolus Ltd. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
The major challenges of CAR-T therapy in T-cell malignancies. (A) Fratricide, in which CAR-T expressing the target antigen are “self killed” by fellow CAR-T. (B) T-cell aplasia, in which normal T cells that also express the target antigen are killed by the CAR-T in “on-target, off-tumor” toxicity. (C) Product contamination, the risk that T lymphoblasts contaminate the final CAR-T product.
Figure 2.
Figure 2.
Summary of potential strategies for overcoming fratricide, T-cell aplasia, and product contamination. G-D, gamma-delta.
See this image and copyright information in PMC

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