Research ArticleCancer

Noncoding regions are the main source of targetable tumor-specific antigens

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Science Translational Medicine  05 Dec 2018:
Vol. 10, Issue 470, eaau5516
DOI: 10.1126/scitranslmed.aau5516

Expanding the landscape of immunotherapy targets

Most searches for druggable tumor-specific antigens (TSAs) start with an examination of peptides derived from protein-coding exons. Laumont et al. took a different approach and found numerous TSAs aberrantly expressed from noncoding sequences in murine cell lines and in B-lineage acute lymphoblastic leukemia and lung cancer patient samples, but not in cells responsible for T cell selection. The authors validated the immunogenicity and efficacy of TSA vaccination for select antigens in mouse models of cancer. The finding that noncoding regions are a potentially rich source of TSAs could greatly expand the number of targetable antigens across different cancers, including those with low mutational burdens.