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通过局部给药实现抗原扩散增强过继性 TCR-T 细胞疗法在胰腺癌中的疗效

英文原题:Antigen Spreading via Localized Administration Enhances Adoptive TCR-T Cell Therapy in Pancreatic Cancer.

PubMed 2026/06/19(内容时间) Adv Sci (Weinh) Q1 · IF 14.1(JCR 2025)

研究概要

癌症疫苗在人类癌症治疗中已显示出初步疗效,但低突变负荷导致肿瘤内缺乏能够介导肿瘤排斥的明确特征性抗原,这仍是胰腺癌面临的一大挑战。

中文摘要

癌症疫苗在人类癌症治疗中已显示出初步疗效,但低突变负荷导致肿瘤内缺乏能够介导肿瘤排斥的明确特征性抗原,这仍是胰腺癌面临的重大挑战。在此,我们介绍一种用于局部肿瘤给药的离子液体ILvax,它能引发全身性、抗原特异性的抗肿瘤免疫反应,从而产生类似疫苗的效果。1型常规树突状细胞(cDC1)是全身免疫反应的决定因素。ILvax消融促进携带肿瘤抗原的cDC1向周围淋巴器官迁移,从而启动cDC1介导的抗原呈递级联反应,导致抗原特异性T细胞反应放大。同时,ILvax诱导的cDC1介导的抗原扩散使过继性TCR-T得以扩增,同时将TCR-T代谢转向氧化磷酸化(OXPHOS)。ILvax局部肿瘤给药同时增强内源性CD8+ T细胞和过继性TCR-T细胞的功能,为胰腺癌提供了一种具有临床转化潜力的协同策略。

展开英文摘要原文

Cancer 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.

论文信息

作者
Huang J、Wang Q、Yao Z、Wang Q、Ji Y、Yang M、Wang M、Shao S
单位
Department of Hepatobiliary and Pancreatic Surgery, School of Medicine, the First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.China
期刊
Advanced science (Weinheim, Baden-Wurttemberg, Germany)2026 Sep
原文标识
PubMed 42318673 · DOI 10.1002/advs.76135