Vaccination with MICA/B alpha 3 domain for the treatment of cancer
The present invention provides compositions and methods for treating cancer in a subject by eliciting an immune response against an MIC alpha 3-domain polypeptide.
1. A fusion protein comprising a monomeric ferritin subunit protein fused 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, wherein the MIC alpha-3 domain protein comprises 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.
2. The fusion protein of claim 1 , wherein the monomeric ferritin subunit protein is a monomeric subunit of a Helicobacter pylori ferritin protein.
3. The fusion protein of claim 1 , further comprising a Cytosine-Guanosine (CpG) oligonucleotide sequence.
4. A nanoparticle comprising the fusion protein of claim 1 .
5. An immunogenic composition comprising the nanoparticle of claim 4 .
6. The immunogenic composition of claim 5 further comprising GM-CSF.
7. The fusion protein of claim 1 , wherein the MIC alpha-3 domain protein comprises the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4.
8. A nanoparticle comprising the fusion protein of claim 7 .
9. A vaccine comprising the nanoparticle of claim 8 .
10. A method of immunizing a mammalian subject comprising administering to the subject the vaccine of claim 9 in an amount effective to elicit an immune response against the MIC alpha-3 domain protein in the subject.
11. The method of claim 10 , further comprising administering GM-CSF or one or more vaccines specific for an antigen other than a MIC alpha-3 domain antigen.
12. The method of claim 10 , wherein the subject has a cancer associated with overexpression of major histocompatibility complex (MHC) class I chain-related protein A (MICA).
13. The method of claim 12 , wherein the vaccine composition is administered as part of a therapeutic regimen.
14. The method of claim 13 , wherein the therapeutic regimen is radiation therapy, targeted therapy, immunotherapy, or chemotherapy.
15. The method of claim 12 , wherein the subject has tested positive for shed serum MICA.