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

Targeting cancer-specific mutations by T cell receptor gene therapy.
Curr Opin Immunol. 2015 Feb 26;33C:112-119
Authors: Blankenstein T, Leisegang M, Uckert W, Schreiber H
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 [PubMed - as supplied by publisher]

Source: Current Opinion in Immunology - February 26, 2015 Category: Allergy & Immunology Authors: Blankenstein T, Leisegang M, Uckert W, Schreiber H Tags: Curr Opin Immunol Source Type: research