An adjuvant for in vivo CAR-T therapy potentiation against solid tumors

Sun, Y.; Ma, Y.; Guan, T.; Yan, Y.; Ming, Y.; Huang, X.; Luo, Y.; Cai, J.; Ma, G.; You, F.; Qiu, M.; Chen, J.; Xia, Y.

doi:10.64898/2026.10.30.763005

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bioRxiv · 10.64898/2026.10.30.763005

An adjuvant for in vivo CAR-T therapy potentiation against solid tumors

Sun, Y.·Ma, Y.·Guan, T.·Yan, Y.·Ming, Y.·Huang, X.·Luo, Y.·Cai, J.·Ma, G.·You, F.·Qiu, M.·Chen, J.·Xia, Y.

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Abstract

In vivo CAR-T therapy offers rapid and controllable T-cell engineering but has yet to achieve durable efficacy against solid tumors. Rather than focusing solely on CAR-T cells, we harness the intact immune system via an in vivo CAR-T adjuvant (iCTA). Composed of aluminum-manganese hydrogel, iCTA can form a spatially confined antigenic and immunostimulatory niche in-situ. By coupling controlled antigen exposure with STING-type I interferon signaling, iCTA not only recruited and reactivated CAR-T cells, but engage the CAR-negative immunocytes with enhanced dendritic-cell antigen presentation and mobilized endogenous antigen-specific T-cell responses. Combined with mRNA-LNP-mediated in vivo CAR-T generation, a single administration of iCTA increased CAR+ T-cell abundance in draining lymph nodes and blood by 2-fold. It also increased T and NK cell infiltration, established an IFNgamma-enriched tumor microenvironment, and reduced exhaustion-associated T-cell states. iCTA improved tumor regression and survival, establishing an adjuvant strategy to enhance in vivo CAR-T therapy.

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Sun, Y., Ma, Y., Guan, T., Yan, Y., Ming, Y., Huang, X., Luo, Y., Cai, J., Ma, G., You, F., Qiu, M., Chen, J., Xia, Y.. 2026-11-02. An adjuvant for in vivo CAR-T therapy potentiation against solid tumors. https://doi.org/10.64898/2026.10.30.763005

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