Neoepitope vaccine and immune stimulant combinations and methods

A method of treating a tumor in an individual in need thereof, the method comprising:

• administering to the individual a first dose of a vaccine composition comprising at least four tumor neoepitope peptides or a nucleic acid encoding at least four tumor neoepitope peptides as a prime vaccination;
• wherein the tumor neoepitope peptides are determined by 1) whole genome sequencing of the individual's tumor and normal DNA, wherein 9-mer neoepitope peptides are identified as being encoded by the tumor DNA, 2) selecting from the neoepitope peptides those encoded by RNA with the greatest expression levels, and 3) selecting 9-mer neoepitope peptides for predicted binding affinity of <500nM for the HLA-type of the individual;
• administering to the individual Alt-803 after the prime vaccination;
• administering to the individual a PDL1 antibody after or concurrently with the Alt-803, wherein the PDL1 antibody is selected from the group consisting of 10F.9G2, atezolizumab, durvalumab, and avelumab;
• administering to the individual a second dose of the vaccine as a boost vaccination;
• and
• administering to the individual an effective amount of IL-12 after the boost vaccination.