Anti-CD7 Fratricide-resistant Chimeric Antigen Receptor T Cells for Relapsed/Refractory Acute Myeloid Leukemia

Researchers at Bambino Gesù Children’s Hospital in Rome have reported that CD7 may be a viable CAR T-cell target in a subset of relapsed or refractory acute myeloid leukemia, and that fratricide-resistant CD7 CAR T cells can induce deep remissions with an encouraging early safety profile. In this Blood study, autologous second-generation CD7-directed CAR T cells were engineered with an anti-CD7 protein expression blocker to prevent self-killing during manufacture and after infusion.The main message is that this approach may open a new cellular therapy option for patients with CD7-positive AML, a group with otherwise very limited treatment options.

The study addresses a major challenge in relapsed or refractory AML, where CAR T-cell development has lagged behind lymphoid malignancies because most candidate targets are shared with normal hematopoietic cells and because antigen expression is highly heterogeneous. CD7 is more commonly associated with T-cell malignancies, but a subset of AML cases also express CD7, raising the possibility that it could serve as a leukemia-associated target in selected patients. The added technical challenge is that T cells themselves express CD7, so unmodified CD7 CAR T cells undergo fratricide. To overcome this, the investigators generated autologous second-generation CD7 CAR T cells incorporating an anti-CD7 protein expression blocker, thereby preventing surface CD7 expression and protecting the engineered cells from self-destruction while preserving antileukemic activity.

Clinically, the strategy was tested in three pediatric or young adult patients with relapsed or refractory CD7-positive AML. All three achieved measurable residual disease negativity after infusion, supporting potent in vivo antileukemic activity in this very high-risk setting. Just as importantly, the reported safety profile was favorable, suggesting that the fratricide-resistant design did not introduce prohibitive toxicity. Although the cohort is very small and longer follow-up will be needed to determine durability, these findings are important because they provide proof of concept that CD7 can be successfully targeted in AML and that fratricide-resistant engineering can make this strategy feasible. Together, the study supports further clinical development of CD7 CAR T cells for biomarker-selected AML patients.

Reference

Becilli M, Merli P, Algeri M, et al. Anti-CD7 fratricide-resistant chimeric antigen receptor T cells for relapsed/refractory acute myeloid leukemia. Blood. Published online March 3, 2026. http://doi.org/10.1182/blood.2025032299

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