Narrative review explores Wnt/β-catenin signaling to improve CAR-T cell persistence in hematologic cancers
This is a narrative review that examines the role of Wnt/β-catenin signaling in T cell development and memory formation, with a focus on its application to CAR-T cell therapy for hematologic cancers. The authors discuss how activation of Wnt/β-catenin signaling arrests effector differentiation and promotes the formation of CD8+ memory stem cells, which are associated with improved CAR-T cell persistence.
The review highlights clinical evidence linking TCF1 and LEF1, downstream effectors of Wnt signaling, to transcriptional and epigenetic memory programming that is important for CAR-T cell persistence and favorable patient outcomes. The authors also describe the clinical potential of Wnt-directed approaches, including genetic, epigenetic, and pharmacological strategies, to improve CAR-T cell memory phenotypes, reduce exhaustion, and enhance persistence.
As a narrative review, the evidence is qualitative and based on the authors' synthesis of existing literature. No pooled effect sizes, sample sizes, or quantitative results are reported. The review does not discuss specific adverse events or safety data. The authors acknowledge that the field is still early, and direct clinical evidence for Wnt-directed CAR-T modifications is limited.
From a practice perspective, the review provides a strong rationale for applying scientific findings from basic T cell biology to CAR-T cell engineering. Clinicians should interpret these findings as hypothesis-generating rather than practice-changing, pending further clinical validation.
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