Neoantigen immunotherapies
AssigneeIogenetics, LLC
InventorsJane Homan, Robert D. Bremel
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Abstract
This invention provides a method for maximizing the immune response to mutated tumor specific proteins, either by means of stimulation of dendritic cells or T cells in vitro followed by administration of these cells to a patient, or by means of administration of a neoantigen vaccine in which de novo peptides, or their encoding nucleic acids, have been designed to ensure an appropriate level of binding affinity to a particular cancer patient's MHC alleles. This invention further provides for modulating the immune response in an immunopathology other than cancer.
Claims20
A method for treating cancer in a subject comprising designing a group of one or more tumor-specific T-cell stimulating peptides, or nucleic acids encoding T cell stimulating peptides, which have a desired predicted binding affinity for the MHC alleles of the subject, comprising the following steps:
- obtaining a biopsy of the subject's tumor;
- obtaining sequences for proteins in said biopsy;
- identifying proteins from the biopsy containing mutated amino acids and the peptide comprising each of said 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 comprises each of said T cell exposed motifs, 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 said T cell exposed motifs, and in which one or more of 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 said array of alternative peptides which have a desired predicted binding affinity for one or more of the subject's MHC alleles;
- and
- synthesizing said group of one or more selected peptides, or nucleic acids encoding the selected peptides.
Dependencies are inferred from the claim text.