Neoepitope vaccine and immune stimulant combinations and methods

1. 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 PDL 1 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.

2. The method of claim 1 , wherein the prime vaccination and the boost vaccination are between 5 and 10 days apart.

3. The method of claim 1 , wherein the administrations of Alt-803 and IL-12 are between 3-5 days apart.

4. The method of claim 1 , wherein the nucleic acid encoding the tumor neoepitope peptides is in an expression vector selected from the group consisting of a bacterial expression vector, a yeast expression vector, and a viral expression vector.

5. The method of claim 4 , wherein the nucleic acid vaccine composition comprises an adenoviral vector.

6. The method of claim 5 , wherein the adenoviral vector encodes at least four neoepitope peptides.