Combination therapy with neoantigen vaccine

A method of treating melanoma, non-small cell lung cancer, bladder cancer, renal cell carcinoma, or non-Hodgkin's lymphoma (NHL) in a single human subject in need thereof comprising:

• (A) administering to the subject nivolumab or pembrolizumab at an interval of at least every two or three weeks for a period of 2-12 weeks;
• (B) following step (A), administering to the subject a composition at least once every week for a period of 14 weeks, wherein the subject is administered up to five doses of the composition during the period of 1-4 weeks, said composition comprising:
• (i) one or more polypeptides comprising at least two peptide sequences calculated by an HLA peptide binding analysis using a program implemented on a computer system to have a binding affinity to a protein encoded by an HLA allele of the single human subject with an IC50 of less than 500 nM, or
• (ii) one or more polynucleotides encoding the one or more polypeptides of (B)(i);
• wherein the at least two peptide sequences are encoded by a plurality of cancer specific nucleic acid sequences that are identified as being specific to cancer cells of the single human subject based on a comparison of (i) whole genome or whole exome nucleic acid sequencing data from a nucleic acid sample of the human subject's cancer cells and (ii) whole genome or whole exome nucleic acid sequencing data from a nucleic acid sample of the human subject's non-cancer cells, wherein each of the cancer specific nucleic acid sequences of the plurality are present in the genome of cancer cells of the human subject but not in the genome of non-cancer cells of the human subject,
• wherein each of the at least two peptide sequences is present in different proteins expressed by the cancer cells;
• wherein each of the at least two peptide sequences comprises a cancer specific amino acid mutation that is not present in the proteins expressed by the non-cancer cells from the single human subject;
• (C) administering nivolumab or pembrolizumab at the start of step (B), or following step (B), every two or three weeks for a period of at least 13 weeks and up to 104 weeks;
• and
• (D) administering one or more doses of the composition of step (B) during the period of the at least 13 weeks and up to 104 weeks of step (C), wherein the composition of step (B) and nivolumab or pembrolizumab of step (C) are not administered to the single human subject on the same day.