TY - JOUR
T1 - Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers
AU - Bradley, Sherille D.
AU - Talukder, Amjad H.
AU - Lai, Ivy
AU - Davis, Rebecca
AU - Alvarez, Hector
AU - Tiriac, Herve
AU - Zhang, Minying
AU - Chiu, Yulun
AU - Melendez, Brenda
AU - Jackson, Kyle R.
AU - Katailiha, Arjun
AU - Sonnemann, Heather M.
AU - Li, Fenge
AU - Kang, Yaan
AU - Qiao, Na
AU - Pan, Bih Fang
AU - Lorenzi, Philip L.
AU - Hurd, Mark
AU - Mittendorf, Elizabeth A.
AU - Peterson, Christine B.
AU - Javle, Milind
AU - Bristow, Christopher
AU - Kim, Michael
AU - Tuveson, David A.
AU - Hawke, David
AU - Kopetz, Scott
AU - Wolff, Robert A.
AU - Hwu, Patrick
AU - Maitra, Anirban
AU - Roszik, Jason
AU - Yee, Cassian
AU - Lizée, Gregory
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-19141-w
DO - 10.1038/s41467-020-19141-w
M3 - Article
C2 - 33087697
AN - SCOPUS:85093840287
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5332
ER -