Scurr, Martin J. ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
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Abstract
Purpose: Broadly expressed, highly differentiated tumor-associated antigens (TAA) can elicit anti-tumor 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 to patient-matched colonic epithelial cells; tumor cell purification was essential to reveal these genes. Candidate TAA protein expression was confirmed by immunohistochemistry, and pre-existing T cell immunogenicity towards 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 IFN-gamma+ response was markedly magnified by control of immunosuppression with cyclophosphamide in cancer patients. Conclusion: 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 |
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Date Type: | Published Online |
Status: | Published |
Schools: | Advanced Research Computing @ Cardiff (ARCCA) Medicine Systems Immunity Research Institute (SIURI) Wales Cancer Research Centre (WCRC) |
Publisher: | American Association for Cancer Research |
ISSN: | 1078-0432 |
Funders: | Cancer Research Wales, Wellcome Trust, Cancer Research UK, Wales Cancer Research Centre |
Date of First Compliant Deposit: | 11 March 2020 |
Date of Acceptance: | 26 February 2020 |
Last Modified: | 15 Aug 2024 00:26 |
URI: | https://orca.cardiff.ac.uk/id/eprint/130130 |
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