| Title: | Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting. |
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| Authors: | ID Bear, Adham S. (Author)
ID Blanchardt, Tatiana (Author)
ID Cesare, Joseph (Author)
ID Ford, Michael J. (Author)
ID Richman, Lee P. (Author)
ID Xu, Chong (Author)
ID Baroja, Miren L. (Author)
ID McCuaig, Sarah (Author)
ID Costeas, Christina (Author)
ID Gabunia, Khatuna (Author)
ID Scholler, John (Author)
ID Posey, Avery D. (Author)
ID OʹHara, Mark H. (Author)
ID Smole, Anže (Author)
ID Powell, Daniel J. (Author)
ID Garcia, Benjamin A. (Author)
ID Vonderheide, Robert H. (Author)
ID Linette, Gerald P. (Author)
ID Carreno, Beatriz M (Author) |
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| Files: |  URL - Source URL, visit https://www.nature.com/articles/s41467-021-24562-2
 PDF - Presentation file, download (2,25 MB)
MD5: 659B873C04CB53A069F351DAF12EEF05
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | 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. |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 16.07.2021 |
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| Year of publishing: | 2021 |
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| Number of pages: | [15] str., art. 4365 |
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| Numbering: | Vol. 12 |
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| PID: | 20.500.12556/DiRROS-19455  |
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| UDC: | 577.2 |
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| ISSN on article: | 2041-1723 |
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| DOI: | 10.1038/s41467-021-24562-2 |
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| COBISS.SI-ID: | 71248131 |
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| Note: | 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;
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| Publication date in DiRROS: | 19.07.2024 |
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| Views: | 281 |
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| Downloads: | 196 |
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