Therapeutic Cancer Vaccine Containing Tumor-Associated Neoantigens and Immunostimulants in a Delivery System

Abstract

A therapeutic vaccine and a method of cancer treatment by inducing humoral and cellular immune responses against malignant cells is provided. The vaccine comprises a delivery system that incorporates at least one peptide whose sequence encompasses a genetic mutation associated with a malignancy (neoantigen), at least one immunostimulant, and at least one type of lipid molecule.

1 . A therapeutic cancer vaccine comprising:
 at least one neoantigen, wherein the neoantigen comprises a tumor-associated genetic mutation peptide, and wherein the tumor-associated genetic mutation peptide further includes an attachment element selected from the group consisting of a transmembrane domain, a fatty acid linker, and a tryptophan attachment element, wherein the attachment element comprises a peptide sequence of 1 to 30 amino acids;   at least one immunostimulant; and   at least one type of lipid molecule.   
     
     
         2 . The vaccine of  claim 1 , wherein the neoantigen is identified by a genetic sequencing of RNA or DNA contained in a hematologic tumor or a tumor-tissue sample obtained by needle biopsy or surgical excision from one or more tumor sites of a patient. 
     
     
         3 . The vaccine of  claim 1 , wherein the neoantigen is a fusion peptide, wherein the fusion peptide comprises a plurality of different tumor-associated genetic mutations. 
     
     
         4 . The vaccine of  claim 1 , wherein the lipid molecule is selected from the group consisting of phospholipids, glycolipids, cholesterol, and derivatives of the lipid molecules. 
     
     
         5 . The vaccine of  claim 4 , wherein the lipid molecule is a saturated or an unsaturated phospholipid or glycolipid, or any combination thereof. 
     
     
         6 . The vaccine of  claim 1 , wherein the lipid molecule comprises lipid bilayers, and wherein the attachment element integrates with the lipid bilayers. 
     
     
         7 . The vaccine of  claim 1 , wherein the fatty acid linker is attached to the neoantigen by an extension of one or more amino acids to the neoantigen sequence at its N or C-terminus. 
     
     
         8 . The vaccine of  claim 1 , wherein the transmembrane domain attachment element is at least 20 amino acids in length. 
     
     
         9 . The vaccine of  claim 1 , wherein the transmembrane domain attachment element is 30 to 70 amino acids in length. 
     
     
         10 . The vaccine of  claim 1 , wherein the transmembrane domain attachment element is TTEYQVAVAGIVFLLISVLLLSGLTWQRRQRK. 
     
     
         11 . The vaccine of  claim 1 , wherein the tryptophan attachment element comprises at least one tryptophan amino acid. 
     
     
         12 . The vaccine of  claim 11 , wherein the tryptophan attachment element is NRWIT. 
     
     
         13 . The vaccine of  claim 1 , wherein the immunostimulant is a cytokine selected from the group consisting of interleukin 2 (IL-2), GM-CSF, M-CSF, and interferon-gamma (IFN-γ). 
     
     
         14 . The vaccine according to  claim 1 , wherein the immunostimulant is a Toll-like Receptor agonist and/or adjuvant selected from the group consisting of monophosphoryl lipid A, lipid A, and muramyl dipeptide (MDP) lipid conjugate and double stranded RNA. 
     
     
         15 . The vaccine according to  claim 1 , wherein the immunostimulant is a costimulatory membrane protein and/or cell adhesion protein selected from the group consisting of CD80, CD86, and ICAM-1. 
     
     
         16 . The vaccine according to  claim 1 , wherein the neoantigen is selected based upon a predicted affinity for binding to the patient's Major Histocompatibility Complex (MHC). 
     
     
         17 . A method of treating cancer in a patient comprising administering to the patient an effective amount of a therapeutic cancer vaccine according to  claim 1 . 
     
     
         18 . A method of cancer treatment by inducing humoral and cellular immune responses against cancer cells in a patient comprising
 genetically sequencing a tumor-tissue sample from a patient to identify a plurality of neoantigens present in the tumor-tissue sample, and wherein the neoantigens comprise tumor-associated genetic mutation peptides;   selecting at least one neoantigen based upon a predicted affinity for binding to a Major Histocompatibility Complex (MHC) of the patient, wherein MHC proteins on a surface of antigen-presenting cells of the patient bind and present the neoantigens to helper and effector T cells of an immune system of the patient, wherein an immune response is directed to the cancer cells in a patient;   administering to the patient a therapeutically effective amount of a vaccine comprising the neoantigen, wherein the neoantigen comprises a tumor-associated genetic mutation peptide, and wherein the tumor-associated genetic mutation peptide further includes an attachment element selected from the group consisting of a transmembrane domain, a fatty acid linker, and a tryptophan attachment element, wherein the attachment element comprises a peptide sequence of 1 to 30 amino acids; at least one immunostimulant; and at least one type of lipid molecule.   
     
     
         19 . The method according to  claim 18 , wherein the vaccine is administered to the patient at a prescribed dose by intradermal, subcutaneous, intramuscular, intranodal, or intra-tumoral injection, or any combination thereof. 
     
     
         20 . The method according to  claim 18 , wherein the patient receives multiple vaccine injections at separate sites. 
     
     
         21 . The method according to  claim 18 , wherein the patient receives multiple vaccinations at prescribed time intervals.