KPNA2-Mediated MYC Nuclear Import Enhances CAR-T Cell Memory and Potentiates Antitumor Efficacy.

KPNA2-mediated MYC nuclear import significantly enhances CAR-T cell memory and antitumor efficacy in preclinical models.

• Why it matters: Understanding how to promote CAR-T cell memory is crucial for improving durable responses in cancer therapy, as current approaches lack effective strategies to sustain CAR-T cell function.
• What they did: Researchers identified that KPNA2 expression correlates with MYC pathway activation in clinical CAR-T products and demonstrated that KPNA2 facilitates MYC nuclear import, boosting memory formation and cytotoxicity through transcriptomic and epigenomic analyses, along with testing a small molecule, TMS, that enhances KPNA2-MYC interaction.
• The result: The study shows that KPNA2-MYC interaction is a key mechanism for CAR-T cell memory, and pharmacological enhancement with TMS improves MYC nuclear accumulation and antitumor potency, enabling new strategies for T cell therapy optimization.