High-Throughput Identification of Patient-Specific Neoepitopes as Therapeutic Targets for Cancer Immunotherapies

Abstract

Systems and methods are presented that allow for selection of tumor neoepitopes that are filtered for various criteria. In particularly contemplated aspects, filtering includes a step in which the mutation leading to the neoepitope is ascertained as being located in a cancer driver gene.

What is claimed is: 
     
         1 . An immune therapeutic composition, comprising:
 a carrier in admixture with or coupled to (i) a synthetic antibody having binding specificity to a patient specific cancer driver neoepitope, (ii) a synthetic patient specific cancer driver neoepitope, (iii) a nucleic acid encoding the patient specific cancer driver neoepitope, or (iv) a chimeric antigen receptor having binding specificity to the patient specific cancer driver neoepitope.   
     
     
         2 . The immune therapeutic composition of  claim 1 , wherein the carrier comprises a single protein or comprises a pharmaceutically acceptable polymer. 
     
     
         3 . The immune therapeutic composition of  claim 1 , wherein the carrier is an immune competent cell. 
     
     
         4 . The immune therapeutic composition of  claim 3 , wherein the immune competent cell is a CD8+ T cell or a NK cell. 
     
     
         5 . The immune therapeutic composition of  claim 1 , wherein the carrier is a recombinant virus. 
     
     
         6 . The immune therapeutic composition of  claim 1 , further comprising a pharmaceutically acceptable carrier suitable for injection or infusion. 
     
     
         7 . The immune therapeutic composition of  claim 1 , wherein the carrier is in admixture with or coupled to the synthetic antibody having binding specificity to a patient specific cancer driver neoepitope. 
     
     
         8 . The immune therapeutic composition of  claim 1 , wherein the carrier is in admixture with or coupled to the synthetic patient specific cancer driver neoepitope. 
     
     
         9 . The immune therapeutic composition of  claim 1 , wherein the carrier is in admixture with or coupled to the nucleic acid encoding the patient specific cancer driver neoepitope. 
     
     
         10 . The immune therapeutic composition of  claim 1 , wherein the carrier is in admixture with or coupled to the chimeric antigen receptor having binding specificity to the patient specific cancer driver neoepitope. 
     
     
         11 . The immune therapeutic composition of  claim 1 , wherein the patient specific cancer driver neoepitope is an expressed missense based patient- and tumor-specific neoepitope. 
     
     
         12 . Theimmune therapeutic composition of  claim 1 , wherein the patient specific cancer driver neoepitope has a length of between 7 and 20 amino acids. 
     
     
         13 . The immune therapeutic composition of  claim 1 , wherein the patient specific cancer driver neoepitope is an HLA-matched neoepitope with respect to the patient's HLA type. 
     
     
         14 . The immune therapeutic composition of  claim 13 , wherein the patient specific cancer driver neoepitope has an affinity to the patient's HLA type of less than 250 nM. 
     
     
         15 . The immune therapeutic composition of  claim 1 , wherein the cancer driver gene is expressed in a solid tumor tissue. 
     
     
         16 . The immune therapeutic composition of  claim 1 , wherein the cancer driver gene is AURKA, BAP1, BRCA1, BRCA2, CCND3, CCNE1, CDK4, CDK6, CDKN1B, CDKN2A, CDKN2B, EGFR, ERBB2, FBXW7, FGFR1, FGFR2, FGFR3, IGF1R, MDM2, MDM4, MET, NF1, NF2, PTEN, SMARCA4, SMARCB1, STK11, or TP53 
     
     
         17 . The immune therapeutic composition of  claim 1 , wherein the cancer driver gene is expressed in a cancer selected from the group consisting of ALL, AML, BLCA, BRCA, CLL, CM, COREAD, ESCA, GBM, HC, HNSC, LUAD, LUSC, MB, NB, NSCLC, OV, PRAD, RCCC, SCLC, STAD, THCA, and UCEC. 
     
     
         18 . The immune therapeutic composition of  claim 1 , further comprising a non-immune therapeutic drug that targets a protein comprising the cancer driver neoepitope. 
     
     
         19 . A recombinant immune competent cell, comprising a nucleic acid encoding a chimeric antigen receptor having binding specificity to a patient specific cancer driver neoepitope, or encoding the patient specific cancer driver neoepitope. 
     
     
         20 . The recombinant immune competent cell of  claim 19  wherein the immune competent cell is a CD8+ T cell or a NK cell, or an NK92 derivative.