Methods of tumor vaccination

Abstract

A method for treating a tumor or generating an immune response against a tumor in a subject in need including a vaccination step comprising administration of a first composition, and a tumor-marking step comprising administration of a second composition, is provided. The first and second composition each comprises an antigenic polypeptide (e.g., a non-tumor antigen) or a nucleic acid encoding an antigenic polypeptide. Also provided are antigenic polypeptides and compositions for use in methods described herein.

1 . A method for generating an immune response against a tumor in a subject comprising:
 a vaccination step comprising administering a first composition to the subject at a site distal to a tumor site, wherein the first composition comprises a non-tumor antigen or a nucleic acid encoding the non-tumor antigen; and   a tumor-marking step comprising administering a second composition to the subject at the tumor site, wherein the second composition comprises the non-tumor antigen or a nucleic acid encoding the non-tumor antigen,   wherein the time between the vaccination step and the tumor-marking step is between about one day and about 6 months.   
     
     
         2 . The method of  claim 1 , optionally wherein:
 the method further comprises one or more booster steps each comprising administering a booster composition to the subject, wherein the booster composition comprises the non-tumor antigen or a nucleic acid encoding the non-tumor antigen, optionally wherein the one or more booster steps occur prior to the tumor-marking step;   the tumor marking-step comprises administering the second composition into the tumor or proximal to the tumor;   the vaccination step comprises administering the first composition via a route selected from the group consisting of intramuscular, subcutaneous, intravenous, intraarterial, intraperitoneal, intrasternal, intradermal, transcutaneous, transdermal, delivery to the interstitial space of a tissue, and delivery to a non-tumor tissue;   the vaccination step comprises administering the first composition into an organ system that is different than the organ system in which the tumor resides, or the vaccination step comprises administering the first composition at a site contralateral to the tumor;   the tumor is a solid tumor, optionally wherein the solid tumor is glioblastoma or ovarian cancer;   the first composition comprises a dendritic cell comprising the non-tumor antigen or a nucleic acid encoding the non-tumor antigen, optionally wherein the dendritic cell is a CD34-positive, CD1a-positive, and CD83-positive mature dendritic cell, optionally wherein the mature dendritic cell is derived from DCOne;   the second composition is prepared for intratumoral administration;   the second composition comprises a dendritic cell comprising the non-tumor antigen or a nucleic acid encoding the non-tumor antigen, optionally wherein the dendritic cell is a CD34-positive, CD1a-positive, and CD83-positive mature dendritic cell, optionally wherein the mature dendritic cell is derived from DCOne;   the first and second compositions each optionally comprises one or more pharmaceutically-acceptable carriers, adjuvants, excipients and/or diluents;   the subject is a non-tumor antigen-naïve subject, or wherein the subject has previously been exposed to the non-tumor antigen, optionally wherein the subject has previously mounted an immune response against the non-tumor antigen; and/or   the subject is a human, or the subject is a domesticated animal and/or an animal suitable for veterinary healthcare.   
     
     
         3 - 5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the vaccination step comprises intradermally administering the first composition, optionally wherein the first composition is prepared for intradermal injection, optionally wherein the first composition comprises a diluent or solvent acceptable for intradermal injection. 
     
     
         7 - 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the vaccination step comprises intramuscularly administering the first composition, optionally wherein the first composition is prepared for intramuscular injection, optionally wherein the first composition comprises a diluent or solvent acceptable for intramuscular injection. 
     
     
         10 - 13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the vaccination step is performed subsequent to the tumor-marking step, or wherein the tumor-marking step is performed subsequent to the vaccination step, optionally wherein:
 the time between the vaccination step and the tumor-marking step is sufficient for an immune response to be mounted as a result of the vaccination step; and/or   the time between the vaccination step and the tumor-marking step is about 2 days to about 21 days.   
     
     
         15 - 23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the second composition comprises a tumor targeting component, optionally wherein:
 the tumor targeting component is a tumor-specific virus, optionally wherein the tumor-specific virus is an oncolytic virus, optionally wherein the tumor-specific virus comprises the non-tumor antigen or a nucleic acid encoding the non-tumor antigen; or   the tumor targeting component is a tumor-specific nanoparticle, optionally wherein the tumor-specific nanoparticle comprises the non-tumor antigen or a nucleic acid encoding the non-tumor antigen.   
     
     
         25 - 38 . (canceled) 
     
     
         39 . A method for generating an immune response against a tumor in a subject comprising:
 a vaccination step comprising administering a first composition to the subject at a site distal to a tumor site, wherein the first composition comprises a non-tumor recall antigen or a nucleic acid encoding the non-tumor recall antigen; and   a tumor-marking step comprising administering a second composition to the subject at the tumor site, wherein the second composition comprises the recall antigen or a nucleic acid encoding the recall antigen.   
     
     
         40 . The method of  claim 39 , optionally wherein:
 the tumor marking-step comprises administering the second composition into the tumor or proximal to the tumor;   the vaccination step comprises administering the first composition via a route selected from the group consisting of intramuscular, subcutaneous, intravenous, intraarterial, intraperitoneal, intrasternal, intradermal, transcutaneous, transdermal, delivery to the interstitial space of a tissue, and delivery to a non-tumor tissue;   the vaccination step comprises administering the first composition into an organ system that is different than the organ system in which the tumor resides, or the vaccination step comprises administering the first composition at a site contralateral to the tumor;   the tumor is a solid tumor, optionally wherein the solid tumor is glioblastoma or ovarian cancer;   the first composition comprises a dendritic cell comprising the recall antigen or a nucleic acid encoding the recall antigen, optionally wherein the dendritic cell is a CD34-positive, CD1a-positive, and CD83-positive mature dendritic cell, optionally wherein the mature dendritic cell is derived from DCOne;   the second composition is prepared for intratumoral administration;   the second composition comprises a dendritic cell comprising the recall antigen or a nucleic acid encoding the recall antigen, optionally wherein the dendritic cell is a CD34-positive, CD1a-positive, and CD83-positive mature dendritic cell, optionally wherein the mature dendritic cell is derived from DCOne   the first and second compositions each optionally comprises one or more pharmaceutically-acceptable carriers, adjuvants, excipients and/or diluents;   the subject has previously been exposed to the recall antigen, optionally wherein the subject has previously mounted an immune response against the recall antigen; and/or   the subject is a human, or the subject is a domesticated animal and/or an animal suitable for veterinary healthcare.   
     
     
         41 . (canceled) 
     
     
         42 . The method of  claim 40 , wherein the vaccination step comprises intradermally administering the first composition, optionally wherein the first composition is prepared for intradermal injection, optionally wherein the first composition comprises a diluent or solvent acceptable for intradermal injection. 
     
     
         43 - 44 . (canceled) 
     
     
         45 . The method of  claim 40 , wherein the vaccination step comprises intramuscularly administering the first composition, optionally wherein the first composition is prepared for intramuscular injection, optionally wherein the first composition comprises a diluent or solvent acceptable for intramuscular injection. 
     
     
         46 - 49 . (canceled) 
     
     
         50 . The method of  claim 39 , wherein the vaccination step and the tumor-marking step are temporally separated, wherein the vaccination step is performed subsequent to the tumor-marking step, or the tumor-marking step is performed subsequent to the vaccination step,
 optionally wherein the time between the vaccination step and the tumor-marking step is sufficient for an immune response to be mounted as a result of the vaccination step,   optionally wherein the time between the vaccination step and the tumor-marking step is about 2 days to about 21 days.   
     
     
         51 - 60 . (canceled) 
     
     
         61 . The method of  claim 39 , wherein the second composition comprises a tumor targeting component, optionally wherein:
 the tumor targeting component is a tumor-specific virus, optionally wherein the tumor-specific virus is an oncolytic virus, optionally wherein the tumor-specific virus comprises the recall antigen or a nucleic acid encoding the recall antigen;   the tumor targeting component is a tumor-specific nanoparticle, optionally wherein the tumor-specific nanoparticle comprises the recall antigen or a nucleic acid encoding the recall antigen.   
     
     
         62 - 74 . (canceled) 
     
     
         75 . A method for generating an immune response against a tumor in a subject comprising:
 a vaccination step comprising administering a first composition to the subject at a site distal to a tumor site, wherein the first composition comprises a diphtheria toxin or detoxified variant thereof or a nucleic acid encoding the diphtheria toxin or detoxified variant thereof; and   a tumor-marking step comprising administering a second composition to the subject at the tumor site, wherein the second composition comprises a diphtheria toxin or detoxified variant thereof or a nucleic acid encoding the diphtheria toxin or detoxified variant thereof.   
     
     
         76 . The method of  claim 75 , optionally wherein:
 the method further comprises one or more booster steps each comprising administering a booster composition to the subject, wherein the booster composition comprises the diphtheria toxin or detoxified variant thereof or a nucleic acid encoding the diphtheria toxin or detoxified variant thereof, optionally wherein the one or more booster steps occur prior to the tumor-marking step;   the diphtheria toxin or detoxified variant thereof is CRM197;   the tumor marking-step comprises administering the second composition into the tumor or proximal to the tumor;   the vaccination step comprises administering the first composition via a route selected from the group consisting of intramuscular, subcutaneous, intravenous, intraarterial, intraperitoneal, intrasternal, intradermal, transcutaneous, transdermal, delivery to the interstitial space of a tissue, and delivery to a non-tumor tissue;   the vaccination step comprises administering the first composition into an organ system that is different to the organ system in which the tumor resides;   the vaccination step comprises administering the first composition at a site contralateral to the tumor;   the tumor is a solid tumor, optionally wherein the solid tumor is glioblastoma or ovarian cancer;   the first composition comprises a dendritic cell comprising CRM197 or a nucleic acid encoding CRM197, optionally wherein the dendritic cell is a CD34-positive, CD1a-positive, and CD83-positive mature dendritic cell, optionally wherein the mature dendritic cell is derived from DCOne;   the second composition is prepared for intratumoral administration;   the second composition comprises a dendritic cell comprising CRM197 or a nucleic acid encoding CRM197, optionally wherein the dendritic cell is a CD34-positive, CD1a-positive, and CD83-positive mature dendritic cell, optionally wherein the mature dendritic cell is derived from DCOne;   the first and second compositions each optionally comprises one or more pharmaceutically-acceptable carriers, adjuvants, excipients and/or diluents; and/or   the subject is a human or the subject is a domesticated animal and/or an animal suitable for veterinary healthcare.   
     
     
         77 - 80 . (canceled) 
     
     
         81 . The method of  claim 75 , wherein the vaccination step comprises intradermally administering the first composition, optionally wherein the first composition is prepared for intradermal injection, optionally wherein the first composition comprises a diluent or solvent acceptable for intradermal injection. 
     
     
         82 - 83 . (canceled) 
     
     
         84 . The method of  claim 75 , wherein the vaccination step comprises intramuscularly administering the first composition, optionally wherein the first composition is prepared for intramuscular injection, optionally wherein the first composition comprises a diluent or solvent acceptable for intramuscular injection. 
     
     
         85 - 88 . (canceled) 
     
     
         89 . The method of  claim 75 , wherein the vaccination step and the tumor-marking step are temporally separated, optionally wherein the vaccination step is performed subsequent to the tumor-marking step, or wherein the tumor-marking step is performed subsequent to the vaccination step,
 optionally wherein the time between the vaccination step and the tumor-marking step is sufficient for an immune response to be mounted as a result of the vaccination step,   optionally wherein the time between the vaccination step and the tumor-marking step is about 2 days to about 21 days.   
     
     
         90 - 99 . (canceled) 
     
     
         100 . The method of  claim 75 , wherein the second composition comprises a tumor targeting component, optionally wherein:
 the tumor targeting component is a tumor-specific virus, optionally wherein the tumor-specific virus is an oncolytic virus, optionally wherein the tumor-specific virus comprises CRM197 or a nucleic acid encoding CRM197; or   the tumor targeting component is a tumor-specific nanoparticle, optionally wherein the tumor-specific nanoparticle comprises CRM197 or a nucleic acid encoding CRM197.   
     
     
         101 - 115 . (canceled)