Department of Melanoma Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA.
Department of Hematopathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Nat Commun. 2020 Oct 21;11(1):5332. doi: 10.1038/s41467-020-19141-w.
Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regressions by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from 35 PDAC patient tumors. This identified a shared HLA-A0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1) as a putative TAA demonstrating overexpression in multiple tumor types and low or absent expression in essential normal tissues. Here we show that VGLL1-specific CTLs expanded from the blood of a PDAC patient could recognize and kill in an antigen-specific manner a majority of HLA-A0101 allogeneic tumor cell lines derived not only from PDAC, but also bladder, ovarian, gastric, lung, and basal-like breast cancers. Gene expression profiling reveals VGLL1 as a member of a unique group of cancer-placenta antigens (CPA) that may constitute immunotherapeutic targets for patients with multiple cancer types.
基于细胞毒性 T 淋巴细胞 (CTL) 的癌症免疫疗法通过靶向肿瘤相关抗原 (TAA) 显示出了诱导临床消退的巨大潜力。为了扩大胰腺导管腺癌 (PDAC) 的 TAA 图谱，我们对来自 35 名 PDAC 患者肿瘤的 HLA Ⅰ类结合肽进行了串联质谱分析。这鉴定出一种源自共转录激活因子 Vestigial-like 1 (VGLL1) 的 HLA-A0101 限制性共享肽，作为一种潜在的 TAA，在多种肿瘤类型中过表达，而在必需的正常组织中低表达或不存在。在这里，我们表明，从一名 PDAC 患者的血液中扩增出的 VGLL1 特异性 CTL 能够以抗原特异性的方式识别和杀伤大多数 HLA-A0101 同种异体肿瘤细胞系，这些细胞系不仅源自 PDAC，还源自膀胱癌、卵巢癌、胃癌、肺癌和基底样乳腺癌。基因表达谱分析显示 VGLL1 是一组独特的癌症胎盘抗原 (CPA) 的成员，这些抗原可能成为多种癌症类型患者的免疫治疗靶点。
