Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer
Abstract
Advanced prostate cancer is a deadly disease made up of multiple cancer subtypes that evolve during its natural history. Unfortunately, antibody- and cell-based therapies in development that target single tumor antigens found in conventional prostate cancer do not account for this heterogeneity. Here, we show that two major subtypes of advanced prostate cancer, prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC), exhibit distinct cell-surface expression profiles. Integrated analysis of gene expression and cell-surface protein expression of prostate cancer nominated multiple subtype-specific cell-surface antigens. We specifically characterize FXYD3 and CEACAM5 as targets for immune-based therapies in PrAd and NEPC and provide preliminary evidence of the antigen-specific cytotoxic activity of CEACAM5-directed chimeric antigen receptor T cells in NEPC.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 23, 2018
- Source ID
- 10.1073/pnas.1802354115
Entities
People
- Ajay Vashisht
- Bryan A. Smith
- Eva Corey
- James Wohlschlegel
- Jiaoti Huang
- John K Lee
- Jung Wook Park
- Nathanael J. Bangayan
- Owen N Witte
- Qingfu Zhang
- Sangwon Yun
- Thomas Graeber
- Tiffany E. Pariva
- Timothy Chai
Organizations
- China Medical University
- Duke University
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles
- National Institutes of Health
- Parker Institute for Cancer Immunotherapy
- Prostate Cancer Foundation
- Stanford University
- Stop Cancer
- United States Department of Defense
- University of California
- University of California, Los Angeles
- University of Washington
- Yale School of Medicine