小柯机器人

美国哈佛医学院免疫学系Kai W. Wucherpfennig研究组研制出一种通过双T细胞和NK细胞攻击来靶向耐药肿瘤的疫苗。2022年5月25日出版的《自然》杂志发表了这项成果。

他们报告了一种癌症疫苗，该疫苗可诱导多种 T 细胞和自然杀伤 (NK) 细胞群的协同攻击。该疫苗针对许多人类癌症因 DNA 损伤而表达的 MICA 和 MICB (MICA/B) 应激蛋白。 MICA/B 作为 T 细胞和 NK 细胞上激活 NKG2D 受体的配体，但肿瘤通过蛋白水解 MICA/B 裂解逃逸免疫识别。疫苗诱导的抗体通过抑制蛋白水解脱落增加肿瘤细胞表面 MICA/B 蛋白的密度，增强树突状细胞向 T 细胞呈递肿瘤抗原并增强 NK 细胞的细胞毒性功能。

值得注意的是，这种疫苗通过 NK 细胞和 CD4+ T 细胞的协同作用，对细胞毒性 T 细胞耐药的主要组织相容性复合物 (MHC) I 类缺陷型肿瘤保持有效。该疫苗在临床上也很有效：手术切除原发性、高度转移性肿瘤后的免疫接种可抑制随后的转移瘤生长。这种疫苗设计甚至可以针对具有常见逃逸突变的肿瘤提供保护性免疫。

据了解，大多数癌症疫苗针对肽抗原，由于将肽呈递给 T 细胞的MHC分子存在巨大的个体差异，因此需要进行个性化。此外，肿瘤经常通过干扰肽呈递的机制逃避 T 细胞介导的免疫。

附：英文原文

Title: A vaccine targeting resistant tumours by dual T cell plus NK cell attack

Author: Badrinath, Soumya, Dellacherie, Maxence O., Li, Aileen, Zheng, Shiwei, Zhang, Xixi, Sobral, Miguel, Pyrdol, Jason W., Smith, Kathryn L., Lu, Yuheng, Haag, Sabrina, Ijaz, Hamza, Connor-Stroud, Fawn, Kaisho, Tsuneyasu, Dranoff, Glenn, Yuan, Guo-Cheng, Mooney, David J., Wucherpfennig, Kai W.

Issue&Volume: 2022-05-25

Abstract: Most cancer vaccines target peptide antigens, necessitating personalization owing to the vast inter-individual diversity in major histocompatibility complex (MHC) molecules that present peptides to T cells. Furthermore, tumours frequently escape T cell-mediated immunity through mechanisms that interfere with peptide presentation1. Here we report a cancer vaccine that induces a coordinated attack by diverse T cell and natural killer (NK) cell populations. The vaccine targets the MICA and MICB (MICA/B) stress proteins expressed by many human cancers as a result of DNA damage2. MICA/B serve as ligands for the activating NKG2D receptor on T cells and NK cells, but tumours evade immune recognition by proteolytic MICA/B cleavage3,4. Vaccine-induced antibodies increase the density of MICA/B proteins on the surface of tumour cells by inhibiting proteolytic shedding, enhance presentation of tumour antigens by dendritic cells to T cells and augment the cytotoxic function of NK cells. Notably, this vaccine maintains efficacy against MHC class I-deficient tumours resistant to cytotoxic T cells through the coordinated action of NK cells and CD4+ T cells. The vaccine is also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumours inhibits the later outgrowth of metastases. This vaccine design enables protective immunity even against tumours with common escape mutations. A vaccine targeting stress proteins expressed by many cancers blocks a tumour escape mechanism, enabling protective immunity mediated by diverse T cell and NK cell populations.

DOI: 10.1038/s41586-022-04772-4

Source: https://www.nature.com/articles/s41586-022-04772-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html