20.500.12556/DiRROS-19455 Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting. Activating RAS missense mutations are among the most prevalent genomic alterations observed in human cancers and drive oncogenesis in the three most lethal tumor types. Emerging evidence suggests mutant KRAS (mKRAS) may be targeted immunologically, but mKRAS epitopes remain poorly defined. Here we employ a multi-omics approach to characterize HLA class I-restricted mKRAS epitopes. We provide proteomic evidence of mKRAS epitope processing and presentation by high prevalence HLA class I alleles. Select epitopes are immunogenic enabling mKRAS-specific TCRαβ isolation. TCR transfer to primary CD8+ T cells confers cytotoxicity against mKRAS tumor cell lines independent of histologic origin, and the kinetics of lytic activity correlates with mKRAS peptide-HLA class I complex abundance. Adoptive transfer of mKRAS-TCR engineered CD8+ T cells leads to tumor eradication in a xenograft model of metastatic lung cancer. This study validates mKRAS peptides as bona fide epitopes facilitating the development of immune therapies targeting this oncoprotein. true false true Angleški jezik Ni določen Neznano 2024-07-18 03:50:38 2024-07-19 10:58:25 2024-07-20 04:03:00 0000-00-00 00:00:00 2021 0 0 Soavtorji: Tatiana Blanchard, Joseph Cesare, Michael J. Ford, Lee P. Richman, Chong Xu, Miren L. Baroja, Sarah McCuaig, Christina Costeas, Khatuna Gabunia, John Scholler, Avery D. Posey Jr., Mark H. OʹHara, Anze Smole, Daniel J. Powell Jr., Benjamin A. Garcia, Robert H. Vonderheide, Gerald P. Linette & Beatriz M. Carreno; Opis vira z dne 22. 7. 2021; Nasl. z nasl. zaslona; art. 4365; [15] str., art. 4365 Vol. 12 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2021-07-16 577.2 2041-1723 10.1038/s41467-021-24562-2 71248131 https://www.nature.com/articles/s41467-021-24562-2 1 6276dc12-4497-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26856 RAZ_Bear_Adham_S._2021.pdf RAZ_Bear_Adham_S._2021.pdf 1 659B873C04CB53A069F351DAF12EEF05 548f6d55b5da2e6678d7132c50571524c0624545e196c8bd787207a8dbba49fa c6286a15-459c-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26980 Nacionalni inštitut za biologijo 0 0 0