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

Autor:	Scurr MJ; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Greenshields-Watson A; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Campbell E; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Somerville MS; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Chen Y; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Hulin-Curtis SL; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Burnell SEA; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Davies JA; Division of Cancer and Genetics, Sir Geraint Evans Building, Cardiff University, Cardiff, United Kingdom., Davies MM; Department of Colorectal Surgery, University Hospital of Wales, Heath Park, Cardiff, United Kingdom., Hargest R; Department of Colorectal Surgery, University Hospital of Wales, Heath Park, Cardiff, United Kingdom., Phillips S; Department of Colorectal Surgery, University Hospital of Wales, Heath Park, Cardiff, United Kingdom., Christian AD; Department of Histopathology, University Hospital of Wales, Heath Park, Cardiff, United Kingdom., Ashelford KE; Division of Cancer and Genetics, Sir Geraint Evans Building, Cardiff University, Cardiff, United Kingdom., Andrews R; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Parker AL; Division of Cancer and Genetics, Sir Geraint Evans Building, Cardiff University, Cardiff, United Kingdom., Stanton RJ; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom., Gallimore A; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom. godkinaj@cardiff.ac.uk gallimoream@cardiff.ac.uk., Godkin A; Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom. godkinaj@cardiff.ac.uk gallimoream@cardiff.ac.uk.; Department of Gastroenterology and Hepatology, University Hospital of Wales, Heath Park, Cardiff, United Kingdom.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Jul 01; Vol. 26 (13), pp. 3360-3370. Date of Electronic Publication: 2020 Mar 02.
DOI:	10.1158/1078-0432.CCR-19-3087
Abstrakt:	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. (©2020 American Association for Cancer Research.)
Databáze:	MEDLINE
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