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

Sherille D. Bradley, Amjad H. Talukder, Ivy Lai, Rebecca Davis, Hector Alvarez, Herve Tiriac, Minying Zhang, Yulun Chiu, Brenda Melendez, Kyle R. Jackson, Arjun Katailiha, Heather M. Sonnemann, Fenge Li, Yaan Kang, Na Qiao, Bih-Fang Pan, Philip L. Lorenzi, Mark Hurd, Elizabeth A. Mittendorf, Christine B. Peterson, Milind Javle, Christopher Bristow, Michael Kim, David A. Tuveson, David Hawke, Scott Kopetz, Robert A. Wolff, Patrick Hwu, Anirban Maitra, Jason Roszik, Cassian Yee () and Gregory Lizée ()
Additional contact information
Sherille D. Bradley: UT MD Anderson Cancer Center
Amjad H. Talukder: UT MD Anderson Cancer Center
Ivy Lai: UT MD Anderson Cancer Center
Rebecca Davis: UT MD Anderson Cancer Center
Hector Alvarez: UT MD Anderson Cancer Center
Herve Tiriac: Cold Spring Harbor Laboratory Cancer Center
Minying Zhang: UT MD Anderson Cancer Center
Yulun Chiu: UT MD Anderson Cancer Center
Brenda Melendez: UT MD Anderson Cancer Center
Kyle R. Jackson: UT MD Anderson Cancer Center
Arjun Katailiha: UT MD Anderson Cancer Center
Heather M. Sonnemann: UT MD Anderson Cancer Center
Fenge Li: UT MD Anderson Cancer Center
Yaan Kang: UT MD Anderson Cancer Center
Na Qiao: UT MD Anderson Cancer Center
Bih-Fang Pan: UT MD Anderson Cancer Center
Philip L. Lorenzi: UT MD Anderson Cancer Center
Mark Hurd: Ahmed Center for Pancreatic Cancer Research, UT MD Anderson Cancer Center
Elizabeth A. Mittendorf: UT MD Anderson Cancer Center
Christine B. Peterson: UT MD Anderson Cancer Center
Milind Javle: UT MD Anderson Cancer Center
Christopher Bristow: Center for Co-clinical Trials, UT MD Anderson Cancer Center
Michael Kim: UT MD Anderson Cancer Center
David A. Tuveson: Cold Spring Harbor Laboratory Cancer Center
David Hawke: UT MD Anderson Cancer Center
Scott Kopetz: UT MD Anderson Cancer Center
Robert A. Wolff: UT MD Anderson Cancer Center
Patrick Hwu: UT MD Anderson Cancer Center
Anirban Maitra: UT MD Anderson Cancer Center
Jason Roszik: UT MD Anderson Cancer Center
Cassian Yee: UT MD Anderson Cancer Center
Gregory Lizée: UT MD Anderson Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19141-w

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