Neoepitope vaccine and immune stimulant combinations and methods

Abstract

Cancer is treated via a coordinated treatment regimen that use various compounds and compositions that employ prime-boost vaccination in combination with immune modulatory treatment and biasing of an immune response towards a Th1 profile.

What is claimed is: 
     
         1 . A composition for use in stimulating an immune response in an individual in need thereof, the composition comprising:
 a. a first dose of a vaccine composition comprising at least one tumor neoepitope peptide or a nucleic acid encoding at least one tumor neoepitope peptide as a prime vaccination; wherein the at least one tumor neoepitope peptide is 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 <500 nM for the HLA-type of the individual;   b. IL-15 or a derivative thereof, for use as an immune stimulant to be administered after the prime vaccination;   c. a checkpoint inhibitor antibody, for use as an immune stimulant to be administered after or concurrently with the IL-15 or derivative thereof;   d. a second dose of the vaccine composition, for use as an immune stimulant to be administered as a boost vaccination; and   e. IL-12, for use as an immune stimulant to be administered after the boost vaccination.   
     
     
         2 . The composition of  claim 1 , wherein the prime vaccination and the boost vaccination are between 1 and 4 weeks apart. 
     
     
         3 . The composition of  claim 1 , further comprising a boost vaccination to be administered at least one month after the first dose of the vaccine composition. 
     
     
         4 . The composition of  claim 1 , further comprising a boost vaccination to be administered at least one year after the first dose of the vaccine composition. 
     
     
         5 . The composition of  claim 1 , wherein the administrations of IL-15 or derivative thereof and IL-12 are between 3-5 days apart. 
     
     
         6 . The vaccine composition 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. 
     
     
         7 . The vaccine composition of  claim 1 , wherein the nucleic acid comprises an adenoviral vector. 
     
     
         8 . The composition of  claim 7 , wherein the adenoviral vector encodes at least four neoepitope peptides. 
     
     
         9 . The composition of  claim 1 , wherein the checkpoint inhibitor antibody comprises a PD-L1 inhibitor, a PD-1 inhibitor, or a CTLA-4 inhibitor. 
     
     
         10 . The composition of  claim 9 , wherein the checkpoint inhibitor antibody comprises a PD-L1 antibody. 
     
     
         11 . The composition of  claim 10 , wherein the PD-L1 antibody is selected from the group consisting of 10F.9G2, atezolizumab, durvalumab, and avelumab. 
     
     
         12 . The composition of  claim 1 , wherein the IL-15 or derivative thereof comprises an IL-15 superagonist. 
     
     
         13 . The composition of  claim 12 , wherein the IL-15 superagonist comprises Alt-803 (N-803).