美国哈佛医学院Mark Cobbold研究组的研究利用抗体介导的病毒表位向肿瘤传递特性，使用CMV特异性T细胞进行癌症治疗。 相关论文2020年2月10日在线发表在《自然—生物技术》杂志上。

研究人员建立了一种免疫疗法，其中非癌抗原的内源性T细胞被重新靶向攻击肿瘤。该方法依赖于使用抗体-肽表位缀合物（APEC）将合适的抗原通过HLA-1递送至肿瘤表面。研究人员使用了APEC对肿瘤杀伤性巨细胞病毒（CMV）特异性CD8 + T细胞重新标记，该APEC包含金属蛋白酶敏感的接头以及肿瘤靶向抗体偶联的CMV衍生抗原决定簇。这些APEC在体外和小鼠癌症模型中重新定义了针对肿瘤细胞的已有CMV免疫。 在体外，APEC可特异性激活效应T细胞的CMV反应，而双特异性T细胞衔接子可激活效应T细胞和调节性T细胞。该方法可能为不适合检查点抑制剂或其他免疫疗法的癌症提供有效的替代治疗方案。

据悉，几种癌症免疫治疗方法，例如免疫检查点封锁和过继T细胞疗法，可增强针对肿瘤的T细胞活性，但这些策略在特异性缺乏针对肿瘤抗原的T细胞中是无效。

附：英文原文

Title: Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy

Author: David G. Millar, Rakesh R. Ramjiawan, Kosuke Kawaguchi, Nisha Gupta, Jiang Chen, Songfa Zhang, Takashi Nojiri, William W. Ho, Shuichi Aoki, Keehoon Jung, Ivy Chen, Feng Shi, James M. Heather, Kohei Shigeta, Laura T. Morton, Sean Sepulveda, Li Wan, Ricky Joseph, Eleanor Minogue, Ashok Khatri, Aditya Bardia, Leif W. Ellisen, Ryan B. Corcoran, Aaron N. Hata, Sara I. Pai, Rakesh K. Jain, Dai Fukumura, Dan G. Duda, Mark Cobbold

Issue&Volume: 2020-02-10

Abstract: Several cancer immunotherapy approaches, such as immune checkpoint blockade and adoptive T-cell therapy, boost T-cell activity against the tumor, but these strategies are not effective in the absence of T cells specific for displayed tumor antigens. Here we outline an immunotherapy in which endogenous T cells specific for a noncancer antigen are retargeted to attack tumors. The approach relies on the use of antibody–peptide epitope conjugates (APECs) to deliver suitable antigens to the tumor surface for presention by HLA-I. To retarget cytomegalovirus (CMV)-specific CD8+ T cells against tumors, we used APECs containing CMV-derived epitopes conjugated to tumor-targeting antibodies via metalloprotease-sensitive linkers. These APECs redirect pre-existing CMV immunity against tumor cells in vitro and in mouse cancer models. In vitro, APECs activated specifically CMV-reactive effector T cells whereas a bispecific T-cell engager activated both effector and regulatory T cells. Our approach may provide an effective alternative in cancers that are not amenable to checkpoint inhibitors or other immunotherapies.

DOI: 10.1038/s41587-019-0404-8

Source: https://www.nature.com/articles/s41587-019-0404-8