PMID- 35474673
OWN - NLM
STAT- MEDLINE
DCOM- 20230823
LR  - 20230823
IS  - 2667-2375 (Electronic)
IS  - 2667-2375 (Linking)
VI  - 1
IP  - 5
DP  - 2021 Sep 27
TI  - Systematic discovery and validation of T cell targets directed against oncogenic 
      KRAS mutations.
PG  - 100084
LID - 10.1016/j.crmeth.2021.100084 [doi]
LID - 100084
AB  - 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      HLA-I molecules using targeted mass spectrometry and identify 13 unpublished 
      KRAS(G12C/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.
CI  - (c) 2021 The Authors.
FAU - Choi, Jaewon
AU  - Choi J
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Goulding, Scott P
AU  - Goulding SP
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Conn, Brandon P
AU  - Conn BP
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - McGann, Christopher D
AU  - McGann CD
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Dietze, Jared L
AU  - Dietze JL
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Kohler, Jessica
AU  - Kohler J
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Lenkala, Divya
AU  - Lenkala D
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Boudot, Antoine
AU  - Boudot A
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Rothenberg, Daniel A
AU  - Rothenberg DA
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Turcott, Paul J
AU  - Turcott PJ
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Srouji, John R
AU  - Srouji JR
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Foley, Kendra C
AU  - Foley KC
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Rooney, Michael S
AU  - Rooney MS
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - van Buuren, Marit M
AU  - van Buuren MM
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Gaynor, Richard B
AU  - Gaynor RB
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Abelin, Jennifer G
AU  - Abelin JG
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Addona, Terri A
AU  - Addona TA
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
FAU - Juneja, Vikram R
AU  - Juneja VR
AD  - BioNTech US Inc., 40 Erie Street, Suite 110, Cambridge, MA 02139, USA.
LA  - eng
PT  - Journal Article
DEP - 20210916
PL  - United States
TA  - Cell Rep Methods
JT  - Cell reports methods
JID - 9918227360606676
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (KRAS protein, human)
MH  - Mice
MH  - Animals
MH  - Humans
MH  - *T-Lymphocytes
MH  - Proto-Oncogene Proteins p21(ras)/genetics
MH  - Mutation
MH  - Receptors, Antigen, T-Cell/genetics
MH  - *Lung Neoplasms/genetics
MH  - Histocompatibility Antigens Class I/genetics
PMC - PMC9017224
OTO - NOTNLM
OT  - HLA
OT  - PRM
OT  - RAS
OT  - T cell
OT  - TCR
OT  - cancer
OT  - immunotherapy
OT  - mass spectrometry
OT  - neoantigen
COIS- J.C., S.P.G., B.P.C., J.L.D., J.K., D.L., D.A.R., P.J.T., J.R.S., K.C.F., M.S.R., 
      M.M.v.B., R.B.G., T.A.A., and V.R.J. are employees and shareholders of BioNTech 
      SE. C.D.McG., A.B., and J.G.A. are former employees of Neon Therapeutics 
      (acquired by BioNTech SE). C.D.McG. is a graduate student at the University of 
      Washington. A.B. is an employee and shareholder of TScan Therapeutics. J.G.A. is 
      an employee of the Broad Institute of MIT and Harvard. R.B.G. is a member of the 
      board of directors at Alkermes plc and Infinity Pharmaceuticals, and a member of 
      the scientific advisory board at Leap Therapeutics.
EDAT- 2022/04/28 06:00
MHDA- 2022/04/28 06:01
PMCR- 2021/09/16
CRDT- 2022/04/27 06:13
PHST- 2020/10/27 00:00 [received]
PHST- 2021/08/04 00:00 [revised]
PHST- 2021/08/20 00:00 [accepted]
PHST- 2022/04/27 06:13 [entrez]
PHST- 2022/04/28 06:00 [pubmed]
PHST- 2022/04/28 06:01 [medline]
PHST- 2021/09/16 00:00 [pmc-release]
AID - S2667-2375(21)00139-9 [pii]
AID - 100084 [pii]
AID - 10.1016/j.crmeth.2021.100084 [doi]
PST - epublish
SO  - Cell Rep Methods. 2021 Sep 16;1(5):100084. doi: 10.1016/j.crmeth.2021.100084. 
      eCollection 2021 Sep 27.