Tumor treatment method with an individualized peptide vaccine
Cancer is treated via a coordinated treatment regimen that use various compounds and compositions that employ a combination vaccination together with immune modulatory treatment and biasing of an immune response towards a Th1 profile.
1. A method of treating a tumor in an individual in need thereof, the method comprising:
administering to the individual a vaccine composition comprising an expression vector that encodes a plurality of filtered tumor peptides, wherein the filtered tumor peptides are determined by 1) comparing omics data from whole genome sequencing of the individual's tumor tissue and normal tissue to identify tumor specific peptides, followed by 2) selecting from the tumor specific peptides those that have high RNA expression levels, and followed by 3) selecting from the highly expressed tumor peptides those that bind to the individual's HLA-type with an affinity of <500 nM to thereby identify the filtered tumor peptides;
administering to the individual Alt-803 after the vaccine composition;
administering to the individual a means for binding PD1 or PDL1 concurrent with or after the Alt-803;
administering a second dose of the vaccine composition; and
administering a Thl stimulation comprising IL12, thereby treating the tumor in the individual.
2. The method of claim 1 , wherein the vaccine composition comprises a single vector encoding the more than one tumor peptide as a single polynucleotide.
3. The method of claim 2 , wherein the more than one tumor peptide consists of 2 to 4 tumor peptides.
4. The method of claim 1 , wherein splenocytes or PBMCs derived from the vaccinated individual are measured ex vivo for IFNg and/or TNFa secretion via ELISPOT assay, whereby stimulation of an T-cell mediated immune response is determined.
5. The method of claim 1 , wherein the tumor peptides are selected from a group consisting of tumor associated antigens, tumor specific antigens and neoepitopes.
6. The method of claim 1 , wherein the IL12 is NHS-IL12.
7. The method of claim 1 , wherein the tumor peptides are 9-mer peptides.
8. The method of claim 1 , wherein RNA expression of neoepitope sequences in tumor tissue is high relative to RNA expression of normal sequences in matched normal tissue.
9. The method of claim 1 , wherein RNA expression of neoepitopes in tumor tissue is high relative to expression of all neoepitopes in tumor tissue.
10. The method of claim 1 , wherein the plurality of encoded peptides comprise peptide sequences of 8-12 amino acids.
11. The method of claim 1 , wherein the plurality of encoded peptides comprise peptide sequences of 20-35 amino acids.
12. The method of claim 1 , wherein patient tumor growth inhibition is determined.
13. The method of claim 1 , wherein the peptides' HLA binding affinities are determined in silico.