Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers.
Antigens, Neoplasm
/ genetics
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ genetics
Carcinoma, Pancreatic Ductal
/ genetics
Cell Line, Tumor
Cytotoxicity, Immunologic
DNA-Binding Proteins
/ genetics
Female
Gene Expression Profiling
HLA-A1 Antigen
/ immunology
Humans
Immunotherapy, Adoptive
Pancreatic Neoplasms
/ genetics
Placenta
/ immunology
Pregnancy
Prognosis
T-Lymphocytes, Cytotoxic
/ immunology
Transcription Factors
/ genetics
Pancreatic Neoplasms
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 10 2020
21 10 2020
Historique:
received:
31
12
2018
accepted:
24
09
2020
entrez:
22
10
2020
pubmed:
23
10
2020
medline:
11
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33087697
doi: 10.1038/s41467-020-19141-w
pii: 10.1038/s41467-020-19141-w
pmc: PMC7577998
doi:
Substances chimiques
Antigens, Neoplasm
0
Biomarkers, Tumor
0
DNA-Binding Proteins
0
HLA-A*01:01 antigen
0
HLA-A1 Antigen
0
Transcription Factors
0
VGLL1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5332Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221707
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218004
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA220236
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
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