Cancer Neoepitopes

Abstract

Contemplated compositions and methods are directed to cancer neoepitopes and uses of such neoepitopes, especially to generate synthetic antibodies against neoepitopes that may then be employed in the manufacture of a therapeutic agent. Preferred therapeutic agents will comprise a synthetic antibody against a neoepitope, and most preferably in combination with a cellular or non-cellular component for use as a diagnostic or therapeutic agent.

What is claimed is: 
     
         1 . A composition comprising a synthetic antibody having binding affinity against a patient—and cancer-specific HLA-matched cancer neoepitope, wherein the neoepitope is unique to the patient and cancer in the patient. 
     
     
         2 . The composition of  claim 1 , wherein the cancer neoepitope is a filtered cancer neoepitope, and wherein the filtered cancer neoepitope is a peptide n-mer having between 5 and 30 amino acids. 
     
     
         3 . The composition of  claim 2 , wherein the cancer neoepitope is characterized by containing a mutation present in a tumor sample relative to a matched normal sample in same patient. 
     
     
         4 . The composition of  claim 3 , wherein the filtered cancer neoepitope is further characterized by a type of mutation, by a strength of expression, and by a predetermined binding affinity towards a HLA-type of the patient. 
     
     
         5 . The composition of  claim 4 , wherein the filtered cancer neoepitope is further filtered by a subcellular location. 
     
     
         6 . The composition of  claim 4 , wherein the HLA-matched cancer neoepitope is matched for MHC-I presentation. 
     
     
         7 . The composition of  claim 4 , wherein the synthetic antibody is selected from the group consisting of an IgG, a F(ab′)2, a Fab′, a Fab, and a scFv. 
     
     
         8 . The composition of  claim 4 , wherein a therapeutic agent is coupled to the synthetic antibody. 
     
     
         9 . The composition of  claim 8 , wherein the therapeutic agent is a non-cellular agent. 
     
     
         10 . The composition of  claim 9 , wherein the non-cellular agent is a chemotherapeutic drug, a radio isotope, a PET detectable isotope, a SPECT detectable isotope, or an affinity agent. 
     
     
         11 . The composition of  claim 8 , wherein the therapeutic agent is a cell. 
     
     
         12 . The composition of  claim 11 , wherein the cell is a T-cell or a NK cell that optionally expresses a genetically modified CD16 receptor. 
     
     
         13 . The composition of  claim 12  wherein the cell is a T-cell expressing a chimeric receptor having a scFv as ectodomain and wherein the synthetic antibody is the scFv. 
     
     
         14 . The composition of  claim 12  wherein the cell is a NK cell expressing a high-affinity Fcγ receptor (CD16) and wherein the synthetic antibody is an IgG and is bound to the NK cell via the high-affinity Fcγ receptor. 
     
     
         15 . A composition comprising:
 a solid phase to which is bound a patient- and cancer-specific HLA-matched cancer neoepitope, wherein the cancer neoepitope is unique to the patient and cancer in the patient;   wherein the cancer neoepitope is a filtered cancer neoepitope;   wherein the filtered cancer neoepitope is a peptide n-mer having between 5 and 30 amino acids;   wherein the cancer neoepitope is characterized by containing a mutation present in a tumor sample relative to a matched normal sample in same patient; and   wherein the filtered cancer neoepitope is further characterized by a type of mutation, by a strength of expression, and by a predetermined binding affinity towards an HLA-type of the patient.   
     
     
         16 . The composition of  claim 15 , wherein the solid phase comprises a wall of a reagent container, a magnetic bead, or an individually addressable element. 
     
     
         17 . The composition of  claim 16 , further comprising a synthetic antibody bound to the cancer neoepitope 
     
     
         18 . The composition of  claim 15 , further comprising a synthetic antibody bound to the cancer neoepitope. 
     
     
         19 . The composition of  claim 18 , wherein the synthetic antibody is selected from the group consisting of an IgG, a F(ab′)2, a Fab′, a Fab, and a scFv. 
     
     
         20 . The composition of  claim 19  wherein the synthetic antibody is coupled to a virus particle.