Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers

• Published in: Nature communications Vol. 11; no. 1; p. 5332
• Main Authors: Bradley, Sherille D., Talukder, Amjad H., Lai, Ivy, Davis, Rebecca, Alvarez, Hector, Tiriac, Herve, Zhang, Minying, Chiu, Yulun, Melendez, Brenda, Jackson, Kyle R., Katailiha, Arjun, Sonnemann, Heather M., Li, Fenge, Kang, Yaan, Qiao, Na, Pan, Bih-Fang, Lorenzi, Philip L., Hurd, Mark, Mittendorf, Elizabeth A., Peterson, Christine B., Javle, Milind, Bristow, Christopher, Kim, Michael, Tuveson, David A., Hawke, David, Kopetz, Scott, Wolff, Robert A., Hwu, Patrick, Maitra, Anirban, Roszik, Jason, Yee, Cassian, Lizée, Gregory
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21-10-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 631/250; 631/61; 631/67; 631/67/1059/2325; 631/67/1059/602; 82/58; 82/75; Adenocarcinoma; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Bladder; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Cancer; Cancer immunotherapy; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - immunology; Carcinoma, Pancreatic Ductal - therapy; Cell Line, Tumor; Cytotoxicity; Cytotoxicity, Immunologic; DNA-Binding Proteins - genetics; DNA-Binding Proteins - immunology; Female; Gene expression; Gene Expression Profiling; Histocompatibility antigen HLA; HLA-A1 Antigen - immunology; Humanities and Social Sciences; Humans; Immunotherapy; Immunotherapy, Adoptive; Lymphocytes; Lymphocytes T; Mass spectrometry; Mass spectroscopy; multidisciplinary; Pancreas; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - therapy; Peptides; Placenta; Placenta - immunology; Pregnancy; Prognosis; Regression analysis; Science; Science (multidisciplinary); T-Lymphocytes, Cytotoxic - immunology; Transcription; Transcription Factors - genetics; Transcription Factors - immunology; Tumor cell lines; Tumors
• ISSN: 2041-1723; 2041-1723
• 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-A*0101 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-A*0101 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.
Cytotoxic T lymphocyte (CTL)-based immunotherapies can induce tumor regressions by targeting HLA class I-bound tumor-associated peptides. Here, the authors identified a peptide derived from Vestigial-like 1 (VGLL1) as a shared, potentially therapeutic CTL target expressed by multiple cancer types.