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

Author

Listed:
  • 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
    UT MD Anderson Cancer Center)

  • Gregory Lizée

    (UT MD Anderson Cancer Center
    UT MD Anderson Cancer Center)

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.

Suggested Citation

  • 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. Sonnem, 2020. "Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19141-w
    DOI: 10.1038/s41467-020-19141-w
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