Cancer Antigen Discovery Is Enabled by RNA Sequencing of Highly Purified Malignant and Nonmalignant Cells

Scurr, Martin J, Greenshields-Watson, Alex, Campbell, Emma, Somerville, Michelle S, Chen, Yuan, Hulin-Curtis, Sarah L ORCID: 0000-0003-0889-964X, Burnell, Stephanie EA, Davies, James A, Davies, Michael M, Hargest, Rachel, Phillips, Simon, Christian, Adam D, Ashelford, Kevin E, Andrews, Robert, Parker, Alan L, Stanton, Richard J, Gallimore, Awen and Godkin, Andrew (2020) Cancer Antigen Discovery Is Enabled by RNA Sequencing of Highly Purified Malignant and Nonmalignant Cells. Clinical Cancer Research, 26 (13). pp. 3360-3370. doi:10.1158/1078-0432.CCR-19-3087

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Text 14142 Scurr, Greenshields-Watson, Campbell, Somerville, Chen, Hulin-Curtis (2020) Cancer antigen discovery is enabled by RNA sequencing of highly purified malignant and nonmalignant cells.pdf - Accepted Version Available under License Creative Commons Attribution 4.0. Download (1MB) | Preview

Abstract

Abstract Purpose: Broadly expressed, highly differentiated tumor-associated antigens (TAA) can elicit antitumor immunity. However, vaccines targeting TAAs have demonstrated disappointing clinical results, reflecting poor antigen selection and/or immunosuppressive mechanisms. Experimental Design: Here, a panel of widely expressed, novel colorectal TAAs were identified by performing RNA sequencing of highly purified colorectal tumor cells in comparison with patient-matched colonic epithelial cells; tumor cell purification was essential to reveal these genes. Candidate TAA protein expression was confirmed by IHC, and preexisting T-cell immunogenicity toward these antigens tested. Results: The most promising candidate for further development is DNAJB7 [DnaJ heat shock protein family (Hsp40) member B7], identified here as a novel cancer-testis antigen. It is expressed in many tumors and is strongly immunogenic in patients with cancers originating from a variety of sites. DNAJB7-specific T cells were capable of killing colorectal tumor lines in vitro, and the IFNγ+ response was markedly magnified by control of immunosuppression with cyclophosphamide in patients with cancer. Conclusions: This study highlights how prior methods that sequence whole tumor fractions (i.e., inclusive of alive/dead stromal cells) for antigen identification may have limitations. Through tumor cell purification and sequencing, novel candidate TAAs have been identified for future immunotherapeutic targeting.

Item Type:	Article
Article Type:	Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Schools and Research Institutes > School of Education and Science
Research Priority Areas:	Health, Life Sciences, Sport and Wellbeing
Depositing User:	Sarah Curtis
Date Deposited:	18 Jun 2024 09:55
Last Modified:	18 Jun 2024 10:00
URI:	https://eprints.glos.ac.uk/id/eprint/14142

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