Figure 1From: Mining the mutanome: developing highly personalized Immunotherapies based on mutational analysis of tumorsHighly personalized medicine. Inexpensive and highly available DNA sequencing can revolutionize cancer immunotherapy by enabling highly personalized approaches involving the identification of new tumor-associated antigens. The expressed genes from a patient’s tumor can be sequenced to identify candidate mutant T cell epitopes. Relevant epitopes that could potentially bind to any given patient’s HLA molecules could be predicted using peptide prediction algorithms (e.g. http://www.syfpeithi.de/bin/MHCServer.dll/EpitopePrediction.htm. Or http://www-bimas.cit.nih.gov/molbio/hla_bind). If peptides derived from mutant proteins are found to capable of forming new HLA-restricted target structures, the candidate peptides can be used in one of at least several ways: 1) “fish out” or sort cells for relevant antigens (such as those specific for driver oncogenes) using tetramer like reagents; 2) use the candidate peptides to stimulate T cell clonotypes already present in a patient’s tumor or in their peripheral blood; 3) use antigens to elicit new T cell receptors in mice that are transgenic for human MHC molecules; and 4) to immunize patients against antigens. If the T cells generated are specific for a patient’s tumor, they can be expanded and adoptively transferred if they are of human origin, or used as a source of TCR for gene engineering approaches.Back to article page