Nant cancer vaccine strategies

Abstract

A patient having cancer can be treated using coordinated treatment regimens based on at least two omics data sets obtained from a solid tumor and a liquid biopsy that may indicates a plurality of tumor status in the patient's body. The treatment regimens can use various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting.

What is claimed is: 
     
         1 . A method of treating a cancer patient, comprising:
 obtaining a first omics data set from a first tumor tissue of the patient and a second omics data set from a second tumor tissue of the patient wherein the first and second tumor tissues are anatomically distinct tumors;   determining a first tumor microenvironment status of the first tumor tissue based on the first omics data set and a second tumor microenvironment status of the second tumor tissue based on the second omics data set;   wherein the first and second tumor microenvironment status are selected from the group consisting of an escape phase, an elimination phase, and an equilibrium phase;   treating the patient with a treatment regimen that is determined based on the first and second phases of the first and second tumor tissues, respectively; and
 wherein the treatment regimen comprises a first pharmaceutical composition that reverts the escape phase by reducing immune suppression in a tumor microenvironment, wherein the first pharmaceutical composition is an inhibitor of an immune suppressive cell, 
 a second pharmaceutical composition that induces the elimination phase by enhancing at least one of an adaptive immune response and an innate immune response, wherein the second pharmaceutical composition comprises a recombinant vaccine composition, and/or 
 a third pharmaceutical composition that maintains the equilibrium phase by biasing the adaptive immune response towards a T H 1 response wherein the third pharmaceutical composition comprises a recombinant vaccine composition and at least one of an immune stimulatory cytokine and a checkpoint inhibitor. 
   
     
     
         2 . The method of  claim 1 , wherein the first and second tumor tissues are originated from a same tumor. 
     
     
         3 . The method of  claim 1 , wherein the first omics data set comprises both genomic and transcriptomic data sets. 
     
     
         4 . The method of  claim 1 , wherein the second omics data set derived from a bodily fluid sample. 
     
     
         5 . The method of  claim 1 , wherein the second omics data set comprises genomic or transcriptomic data set of cell free DNA or cell free RNA present in the bodily fluid. 
     
     
         6 . The method of  claim 1 , wherein the immune suppressive cell is selected from the group consisting of T-reg cell, a myeloid derived suppressor cell, and a M2 macrophage. 
     
     
         7 . The method of  claim 6 , wherein the inhibitor of the immune suppressive cell is administered in a low-dose metronomic fashion. 
     
     
         8 . The method of  claim 6 , wherein the inhibitor of the immune suppressive cell comprises a drug bound to albumin. 
     
     
         9 . The method of  claim 6 , wherein the inhibitor of the immune suppressive cell is further coupled to a tumor targeting antibody. 
     
     
         10 . The method of  claim 6 , wherein the first pharmaceutical composition further comprises a vascular permeability enhancer. 
     
     
         11 . The method of  claim 1 , wherein the recombinant vaccine composition in the second pharmaceutical composition comprises a recombinant bacterial vaccine, recombinant yeast vaccine, or a recombinant viral vaccine. 
     
     
         12 . The method of  claim 11 , wherein the second pharmaceutical composition further comprises an immune stimulatory cytokine. 
     
     
         13 . The method of  claim 12 , wherein the immune stimulatory cytokine is selected from the group consisting of IL-2, IL-15, IL-17, IL-21, and Alt-803. 
     
     
         14 . The method of  claim 1 , wherein the second pharmaceutical composition further comprises a natural killer cell selected form the group consisting of an aNK cell, a haNK cell, and a taNK cell. 
     
     
         15 . The method of  claim 1 , wherein the recombinant vaccine composition in the third pharmaceutical composition comprises a recombinant bacterial vaccine, recombinant yeast vaccine, or a recombinant viral vaccine. 
     
     
         16 . The method of  claim 1 , wherein the checkpoint inhibitor in the third pharmaceutical composition is selected from the group consisting of a PD-1 inhibitor and a CTLA4 inhibitor, and wherein the immune stimulatory cytokine is selected from the group consisting of IL-2, IL-15, IL-17, IL-21, and Alt-803. 
     
     
         17 . The method of  claim 1 , wherein the first tumor microenvironment status is the escape phase and the second tumor microenvironment status is the elimination phase, and wherein the treatment regimen comprises a first pharmaceutical composition that is administered intratumorally to the first tumor tissue and a second pharmaceutical composition that is administered after the first pharmaceutical composition. 
     
     
         18 . The method of  claim 17 , further comprising:
 obtaining a third omics data set from the first tumor tissue of the patient after treating the first tumor tissue with the first pharmaceutical composition;   determining a third tumor microenvironment status of the treated first tumor tissue as elimination phase; and   treating the patient with the second pharmaceutical composition.   
     
     
         19 . The method of  claim 18 , further comprising:
 obtaining a fourth data set from a second sample of the bodily fluid obtained after treating the first tumor tissue with the first pharmaceutical composition;   determining the fourth tumor microenvironment status of the second tumor based on the fourth omics data set; and   adjusting the treatment regimen based on the fourth phase of the second tissue.   
     
     
         20 . The method of  claim 1 , further comprising a step of administering low dose radiation to the first tumor tissue.