Patent ID: 11920202
Assignee: UNIVERSITY OF CONNECTICUT
Field: Measurement (Instruments)
Classification: CPC C  G | IPC C  G

Claim 0:
1. An unbiased method of identifying tumor rejection mediating neoepitopes (TRMNs), comprising:
comparing a cancer cell exome sequence from a cancer patient to a reference exome sequence and identifying single nucleotide variants (SNVs) in the cancer cell exome sequence compared to the reference exome sequence;
validating the SNVs using nucleic acid sequencing;
identifying 8-14 amino acid putative neoepitopes including the validated SNVs, wherein the putative neoepitopes are unbiased by MHC binding and/or CD8T* reactivity;
calculating an IC50 for an MHC allele for each 8-14 amino acid putative neoepitope including the SNVs and calculating an IC50 for the MHC allele for a corresponding non-mutated amino acid sequence for each validated SNV;
plotting the putative neoepitope IC50s on one axis, and the non-mutated amino acid sequence IC50s on a perpendicular axis to provide a bivariate scatter plot;
clustering the putative neoepitopes in the bivariate scatter plot using model-based clustering based on parameterized finite Gaussian mixture models using the IC50s;
selecting as TRMNs the neoepitopes in the bivariate scatter plot which are clustered putative neoepitopes in the space greater than 501 nM on the x-axis and greater than 501 nM on the y-axis
wherein the TRMNs are in an elliptical cluster encompassed by a circle having a center at 27,176.9 nM for the x-axis and 33,556.51 nM for the y-axis, and a radius of 33,195 nM from the center, or
wherein the TRMNs are in an elliptical cluster encompassed by a circle having a center at 27,176.9 nM for the x-axis and 33,556.51 nM for the y-axis and a radius of 22,430 nM from the center;

producing a peptide population or a nucleic acid population for expressing the peptide population, the peptide population comprising 15-100 different amino acid peptides, the peptides including one or more of the TRMNs;
producing a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the peptide population or nucleic acid population; and
optionally administering the pharmaceutical composition to the cancer patient.