Antigen Spreading via Localized Administration Enhances Adoptive TCR‐T Cell Therapy in Pancreatic Cancer

Advanced Science

卷:13

RESEARCH ARTICLE

Junming Huang^1,2  Qin Wang^1,2  Zhuo Yao^1,2  Qing Wang^1,2  Yongtao Ji^1,2  Minqi Yang^1,2  Meng Wang^2,3  Shiyi Shao^1,2  Xinyu Zhao^1,2  Fu Zhang^1,2  Tingbo Liang^1,2,3,4,5,6  Qida Hu^1,2 

[1] Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, the First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China

[2] Department of Breast Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

[3] Zhejiang University Cancer Center, Zhejiang University, Hangzhou, China

[4] The Innovation Center For the Study of Pancreatic Diseases, Hangzhou, China

[5] Department of Hepatobiliary and Pancreatic Surgery, School of Medicine, the First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China

[6] MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou, China

关键词: antigen presentation;    antigen;    cancer;    cancer research;    cd8;    cell therapy;    immune system;    medicine;    pancreatic cancer;   

DOI  :  10.1002/advs.76135

 received in 2026-03-15, accepted in 2026-06-09,  发布年份 2026

来源: Wiley

【 摘 要 】

ABSTRACTCancer vaccines have demonstrated initial effectiveness in the treatment of human cancers, still the low mutational burden, which leads to a deficiency of well‐characterized antigens expressed within tumors capable of mediating tumor rejection, poses a significant challenge in pancreatic cancer. Here, we introduce an ionic liquid ILvax for localized tumor administration, which elicits a systemic and antigen‐specific anti‐tumor immune response, thereby generating a vaccine‐like effect. Type 1 conventional dendritic cells (cDC1) is the determinant for systemic immune response. ILvax ablation facilitates migration of tumor antigen‐carrying cDC1 to peripheral lymphoid organs, thus initiating the cDC1‐mediated antigen presentation cascade that results in an amplified antigen‐specific T cells response. Meanwhile, cDC1‐mediated antigen spreading induced by ILvax enabled the expansion of adoptive TCR‐T while shifting TCR‐T metabolism toward oxidative phosphorylation (OXPHOS). Localized tumor administration with ILvax simultaneously enhances the functionality of both endogenous CD8+ T cells and adoptive TCR‐T cells, offering a clinically translatable collaborative strategy against pancreatic cancer.

【 授权许可】

CC BY   
© 2026 The Author(s). Advanced Science published by Wiley‐VCH GmbH.