Format

Send to

Choose Destination
Curr Opin Immunol. 2015 Apr;33:112-9. doi: 10.1016/j.coi.2015.02.005. Epub 2015 Feb 27.

Targeting cancer-specific mutations by T cell receptor gene therapy.

Author information

1
Max-Delbrück-Center for Molecular Medicine, 13092 Berlin, Germany; Institute of Immunology, Charité Campus Buch, 13125 Berlin, Germany. Electronic address: tblanke@mdc-berlin.de.
2
Institute of Immunology, Charité Campus Buch, 13125 Berlin, Germany.
3
Max-Delbrück-Center for Molecular Medicine, 13092 Berlin, Germany; Institute of Biology, Humboldt University Berlin, 10115 Berlin, Germany.
4
Institute of Immunology, Charité Campus Buch, 13125 Berlin, Germany; Department of Pathology, Committee on Immunology and Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA.

Abstract

The ease of sequencing the cancer genome, identifying all somatic mutations and grafting mutation-specific T cell receptor (TCR) genes into T cells for adoptive transfer allow, for the first time, a truly tumor-specific and effective therapy. Mutation-specific TCR gene therapy might achieve optimal efficacy with least possible toxicity. Recent clinical data confirm the long-standing evidence from experimental cancer models that antigens encoded by the tumor-specific somatic mutations are potentially the best targets for adoptive T cell therapy. Open questions are, how many somatic mutations create suitable epitopes, whether only individual-specific or also recurrent somatic mutations qualify as suitable epitopes and how neoantigen-specific TCRs are most efficiently obtained. Tumor heterogeneity needs to be considered; therefore, it will be important to identify immunogenic driver mutations that occurred early, are essential for cancer cell survival and present in all cancer cells.

PMID:
25728991
PMCID:
PMC4557613
DOI:
10.1016/j.coi.2015.02.005
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center