Systematic discovery and validation of T cell targets directed against oncogenic KRAS mutations.
Cell Rep Methods
; 1(5): 100084, 2021 09 27.
Article
in En
| MEDLINE
| ID: mdl-35474673
ABSTRACT
Oncogenic mutations in KRAS can be recognized by T cells on specific class I human leukocyte antigen (HLA-I) molecules, leading to tumor control. To date, the discovery of T cell targets from KRAS mutations has relied on occasional T cell responses in patient samples or the use of transgenic mice. To overcome these limitations, we have developed a systematic target discovery and validation pipeline. We evaluate the presentation of mutant KRAS peptides on individual HLA-I molecules using targeted mass spectrometry and identify 13 unpublished KRASG12C/D/R/V mutation/HLA-I pairs and nine previously described pairs. We assess immunogenicity, generating T cell responses to nearly all targets. Using cytotoxicity assays, we demonstrate that KRAS-specific T cells and T cell receptors specifically recognize endogenous KRAS mutations. The discovery and validation of T cell targets from KRAS mutations demonstrate the potential for this pipeline to aid the development of immunotherapies for important cancer targets.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Lung Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep Methods
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos