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. Author manuscript; available in PMC: 2019 Aug 16.
Published in final edited form as: N Engl J Med. 2017 Feb 16;376(7):e11.

T-Cell Transfer Therapy Targeting Mutant KRAS

Andrew J Rech 1, Robert H Vonderheide 1
PMCID: PMC6697099  NIHMSID: NIHMS1039501  PMID: 28199803

TO THE EDITOR:

Tran et al. (Dec. 8 issue)1 describe a remarkable case of a patient with metastatic colorectal cancer treated with autologous T cells specific for mutant KRAS G12D and restricted to the major histocompatibility complex class I allele HLA-C*08:02. The authors hypothesize that in the United States alone, thousands of patients per year may be eligible for T-cell–based immunotherapy targeting KRAS G12D. To estimate how common this opportunity may be, we identified 151 patients with KRAS G12D mutations out of 6125 patients in the Cancer Genome Atlas. Of these, only 4 had the HLA-C*08:02 allele as determined by a validated computational method.2,3

We then investigated immune activity in tumor samples using established gene signatures.4,5 Comparing KRAS G12D–positive tumors with disease-matched KRAS wild-type tumors, we found no evidence of unique immune activity. Nor did we find evidence of unique immune activity in patients with the HLA-C*08:02 allele, regardless of KRAS mutation status.

Immunotherapy targeting KRAS G12D in patients with the HLA-C*08:02 allele appears to be an important but rare opportunity. Evaluation of other KRAS mutations and alleles is warranted.

Footnotes

No potential conflict of interest relevant to this letter was reported.

References

  • 1.Tran E, Robbins PF, Lu Y-C, et al. T-cell transfer therapy targeting mutant KRAS in cancer. N Engl J Med 2016;375:2255–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
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