Journal of hematology & oncologyOct 24, 2025

Genome-edited donor CAR-T cells as the next generation of cancer immunotherapy

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Genome-edited allogeneic CAR-T cells may make cancer immunotherapy more scalable, but core safety and manufacturing barriers remain.

Evidence

This review summarizes universal donor-derived CAR-T approaches, tools including ZFNs, TALENs, CRISPR systems, base editing, and prime editing, and early clinical trial progress.

Caveat

Clinical implementation is still limited by , , off-target effects, genotoxicity, and manufacturing scalability.

Simplified

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in technologies and promising clinical trial data, significant challenges remain, including (GVHD), (HVGR), off-target effects, genotoxicity, and manufacturing scalability. To address these concerns, genome-editing technologies such as ZFNs, TALENs, Meganucleases, CRISPR systems, base editing, and prime editing are being employed. This review summarizes the progress of universal allogeneic CAR-T cell therapies, addresses the critical challenges, and discusses the future directions for their clinical implementation.

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Genome-edited donor CAR-T cells as the next generation of cancer immunotherapy

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