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

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 (October 2020) Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers. Nature Communications, 11 (1). p. 5332. ISSN 2041-1723

PDF 2020.Bradley.VestigialLike1.pdf Download (1MB)

Abstract

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.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment diseases & disorders > neoplasms bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification Investigative techniques and equipment > biomarker diseases & disorders > cancer > cancer types > breast cancer organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > cancer > drugs and therapies > Immunotherapy organs, tissues, organelles, cell types and functions diseases & disorders > cancer > cancer types > pancreatic cancer diseases & disorders > pregnancy bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Tiriac, Herve Tuveson, David A.
Communities:	CSHL labs > Tuveson lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	21 October 2020
Date Deposited:	06 May 2021 18:33
Last Modified:	29 Jan 2024 20:30
PMCID:	PMC7577998
URI:	https://repository.cshl.edu/id/eprint/40022

Actions (login required)

Administrator's edit/view item