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.
Highlights
The cancer mutanome: is it important? Peptides encoded by mutated genes in cancer cells have long been recognized as potential T cell targets, yet they were not pursued for personalized cancer therapy due to time and cost constraints on their identification
The recent arrival of next-generation sequencing and bioinformatics approaches allows, for the first time, the rapid and affordable elucidation of an individual cancer patient’s genome, exome, epigenome and transcriptome at the single nucleotide level [1]. This in turn enables the identification of patient-specific omic alterations that can function as unique therapeutic targets such as neoantigens [2,3,4,5,6,7,8] (Figure 1)
Several very exciting recent reports on the power of immunity against m-peptides to shrink tumors in mice and patients suggest the importance of understanding the biology of m-peptides and their application in immunotherapy
Summary
Mining the mutanome: developing highly personalized Immunotherapies based on mutational analysis of tumors. Willem W Overwijk1*, Ena Wang, Francesco M Marincola, Hans-Georg Rammensee, Nicholas P Restifo and for the Organizing Committee of the 2013 SITC Workshop on Personalized Immunotherapy
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