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Open Access Highly Accessed Review

Mining the mutanome: developing highly personalized Immunotherapies based on mutational analysis of tumors

Willem W Overwijk1*, Ena Wang2, Francesco M Marincola23, Hans-Georg Rammensee4, Nicholas P Restifo56 and for the Organizing Committee of the 2013 SITC Workshop on Personalized Immunotherapy

Author Affiliations

1 Department of Melanoma Medical Oncology, The University of Texas M.D, Anderson Cancer Center, Houston, TX, USA

2 Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

3 Sidra Medical and Research Centre, Doha, Qatar

4 Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany

5 Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

6 NIH Center for Regenerative Medicine, National Institutes of Health, Bethesda, MD, USA

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Journal for ImmunoTherapy of Cancer 2013, 1:11  doi:10.1186/2051-1426-1-11

Published: 29 July 2013

Abstract

T cells can mediate remarkable tumor regressions including complete cure in patients with metastatic cancer. Genetic alterations in an individual’s cancer cells (the mutanome) encode unique peptides (m-peptides) that can be targets for T cells. The recent advances in next-generation sequencing and computation prediction allows, for the first time, the rapid and affordable identification of m-peptides in individual patients. Despite excitement about the extended spectrum of potential targets in personalized immunotherapy, there is no experience or consensus on the path to their successful clinical application. Major questions remain, such as whether clinical responses to cytokine therapy, T cell transfer, and checkpoint blockade are primarily mediated by m-peptide-specific reactivity, whether m-peptides can be effectively used as vaccines, and which m-peptides are most potently recognized. These and other technological, immunological and translational questions will be explored during a 1-day Workshop on Personalized Cancer Immunotherapy by the Society for Immunotherapy of Cancer, directly before the Annual Meeting, on November 7, 2013 at the National Harbor, MD near Washington, DC.

Keywords:
Mutanome; Mutation; Neoantigen; Peptide epitope; T lymphocyte; Checkpoint blockade; Exome; Vaccine; Next-generation sequencing; Omics