Vaccination with mica/b alpha 3 domain for the treatment of cancer

Abstract

The present invention provides compositions and methods for treating cancer in a subject by eliciting an immune response against a MIC alpha 3-domain polypeptide.

What is claimed is: 
     
         1 . A vaccine composition comprising, as an immunogenic component, an effective amount of a peptide comprising or consisting of the MIC alpha 3-domain, the effective amount being an amount effective to elicit an immune response against the MIC alpha 3-domain. 
     
     
         2 . The vaccine composition of  claim 1 , wherein the MIC alpha 3-domain is a MICA or MICB alpha 3-domain. 
     
     
         3 . The vaccine composition of  claim 1  or  2 , wherein the MIC alpha 3-domain is non glycosylated. 
     
     
         4 . The vaccine composition of any one of  claims 1 - 3 , wherein the peptide comprises or consists of the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4, or an amino acid sequence that is at least 90% identical thereto. 
     
     
         5 . The vaccine composition of any one of  claims 1 - 4 , wherein the vaccine composition comprises a plurality of peptides. 
     
     
         6 . The vaccine composition of any one of  claims 1 - 5 , wherein the peptide is conjugated to carrier protein. 
     
     
         7 . The vaccine composition of  claim 1  further comprising GM-CSF. 
     
     
         8 . A fusion protein comprising a monomeric ferritin subunit protein joined to a MIC alpha 3-domain protein, wherein the monomeric ferritin subunit protein comprises a domain that allows the fusion protein to self-assemble into nanoparticles. 
     
     
         9 . The fusion protein of  claim 8 , wherein the monomeric subunit is a monomeric subunit of a  Helicobacter pylori  ferritin protein. 
     
     
         10 . The fusion protein of  claim 8  or  9 , further comprising a Cytosine-Guanosine (CpG) oligonucleotide sequence. 
     
     
         11 . A nanoparticle comprising the fusion protein of any one of  claims 8 - 10 . 
     
     
         12 . A nanoparticle comprising a plurality of MIC alpha 3-domain peptides. 
     
     
         13 . A vaccine composition comprising the nanoparticle of  claim 11  or  12 . 
     
     
         14 . The vaccine composition of  claim 13 , further comprising GM-CSF. 
     
     
         15 . A method of treating cancer in a subject, the method comprising administering to a subject a composition of any one of  claim 1 - 13 . 
     
     
         16 . The method of  claim 15 , further comprising administering GM-C S F. 
     
     
         17 . The method of  claim 15  or  16 , wherein the composition is administered as part of a therapeutic regimen. 
     
     
         18 . The method of  claim 17 , wherein the therapeutic regimen is radiation therapy, targeted therapy, immunotherapy, or chemotherapy. 
     
     
         19 . The method of any one of  claims 15 - 18 , wherein said subject has tested positive for shed MIC in their serum. 
     
     
         20 . The method of any one of  claims 15 - 19 , comprising administering to the subject one or more vaccines specific for an antigen other than a MIC alpha 3-domain antigen. 
     
     
         21 . A method for treating cancer comprising administering to said subject a vaccine comprising cells that express MIC alpha-3 domain. 
     
     
         22 . A method for treating cancer where an immune response against MIC is induced by use of a replicating or non-replicating virus. 
     
     
         23 . A method of preventing the progression of cancer, the method comprising administering to a subject a composition of any one of  claims 1 - 14 . 
     
     
         24 . The method of  claim 23 , wherein preventing the progression of cancer comprises preventing metastasis of the cancer or delaying tumor growth. 
     
     
         25 . The method of  claim 23 , wherein said subject has tested positive for shed MIC in their serum. 
     
     
         26 . The method of  claim 23 , wherein the cancer is associated with overexpression of MICA. 
     
     
         27 . A method of causing clinical regression of cancer, the method comprising administering to a subject a composition of any one of  claims 1 - 14 . 
     
     
         28 . The method of  claim 27 , wherein said subject has tested positive for shed MIC in their serum. 
     
     
         29 . The method of  claim 27 , wherein the cancer is associated with overexpression of MICA. 
     
     
         30 . A method of eliciting an immune response against the MIC alpha 3-domain, the method comprising administering to a subject a composition of any one of  claims 1 - 14 . 
     
     
         31 . The method of  claim 30 , wherein the composition elicits an immune response against the MIC alpha 3-domain, but not against the MIC alpha 1-domain or MIC alpha 2-domain. 
     
     
         32 . The method of  claim 30 , wherein said subject has tested positive for shed MIC in their serum. 
     
     
         33 . The method of  claim 30 , wherein the cancer is associated with overexpression of MICA.