Personalized allogeneic immunotherapy

A method of treating a subject affected by cancer by providing tumor-mutation specific T cells from an MHC allele-matched donor, comprising the following steps:

• obtaining a biopsy of the subject's tumor;
• obtaining sequences for proteins in the biopsy;
• identifying proteins from the biopsy containing mutated amino acids and the peptide comprising each of the mutated amino acids;
• determining T cell exposed motifs which comprise mutated amino acids in each of the proteins;
• determining the predicted binding affinity to the subject's MHC alleles of peptides which comprise each of the T cell exposed motifs comprising mutated amino acids, or a subset thereof;
• generating an array of alternative peptides not present in the tumor, wherein each peptide in the array comprises the amino acids of one of the T cell exposed motifs, and in which the amino acids not within the T cell exposed motif are substituted to change the predicted MHC binding affinity;
• selecting a group of one or more selected peptides from the array of alternative peptides which have a desired predicted binding affinity for one or more of the subject's MHC alleles;
• and
• synthesizing the group of one or more selected peptides, or nucleic acids encoding the selected peptides;
• and
• obtaining T cells from a donor who carries at least one matched MHC allele to the subject;
• and
• contacting dendritic cells in vitro with the selected peptides, or nucleic acids encoding the selected peptide, then contacting the dendritic cells with the T cells from the donor;
• and
• multiplying in vitro the T cells responsive to the selected peptide;
• and infusing the T cells responsive to the selected peptide from the donor into the subject.