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Targeting cancer-specific mutations by T cell receptor gene therapy

Item Type:Review
Title:Targeting cancer-specific mutations by T cell receptor gene therapy
Creators Name:Blankenstein, T. and Leisegang, M. and Uckert, W. and 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.
Keywords:Adoptive Immunotherapy, Histocompatibility Antigens Class I, Mutation, Neoplasm Antigens, Neoplasms, Protein Binding, Recombinant Fusion Proteins, T-Cell Antigen Receptor Specificity, T-Cell Antigen Receptors, T-Lymphocyte Epitopes, T-Lymphocyte Subsets, Treatment Outcome, Animals
Source:Current Opinion in Immunology
ISSN:0952-7915
Publisher:Current Biology (U.K.)
Volume:33
Page Range:112-119
Date:April 2015
Official Publication:https://doi.org/10.1016/j.coi.2015.02.005
PubMed:View item in PubMed

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