Nature Communications (Jul 2021)
Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting
- Adham S. Bear,
- 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,
- Mark H. O’Hara,
- Anze Smole,
- Daniel J. Powell,
- Benjamin A. Garcia,
- Robert H. Vonderheide,
- Gerald P. Linette,
- Beatriz M. Carreno
Affiliations
- Adham S. Bear
- Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania
- Tatiana Blanchard
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- Joseph Cesare
- Department of Biochemistry and Biophysics, University of Pennsylvania
- Michael J. Ford
- MSBioworks
- Lee P. Richman
- Abramson Cancer Center, University of Pennsylvania
- Chong Xu
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- Miren L. Baroja
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- Sarah McCuaig
- Perelman School of Medicine, University of Pennsylvania
- Christina Costeas
- Perelman School of Medicine, University of Pennsylvania
- Khatuna Gabunia
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- John Scholler
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- Avery D. Posey
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- Mark H. O’Hara
- Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania
- Anze Smole
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- Daniel J. Powell
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- Benjamin A. Garcia
- Department of Biochemistry and Biophysics, Epigenetics Institute, University of Pennsylvania
- Robert H. Vonderheide
- Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania
- Gerald P. Linette
- Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania
- Beatriz M. Carreno
- Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania
- DOI
- https://doi.org/10.1038/s41467-021-24562-2
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 16
Abstract
KRAS is commonly mutated at codon 12 in several cancer types, offering a unique opportunity for the development of neoantigen-targeted immunotherapy. Here the authors present a pipeline for the prediction, identification and validation of HLA class-I restricted mutant KRAS G12 peptides, leading to the generation of mutant KRAS-specific T cell receptors for adoptive T cell immunotherapy.