![]() ![]() MIC (the term “MIC” referring to MICA and MICB) shedding is accomplished in part through interactions with the protein disulfide isomerase ERp5, which cleaves a disulfide bond in the MIC a3 domain, rendering it susceptible to proteolysis by ADAM-10/17 and MMP14. MHC class I chain related protein A and B are NKG2D ligand shed from tumor cells, i.e., released from the cell surface into the surrounding medium, and sera from a subset of cancer patients contains elevated levels of the soluble form (sMICA). This invention relates generally methods of treating cancer by inhibition of shedding of NKG2D ligands such MHC class I chain related protein A and B. 62/001,571 filed May 21, 2014, the contents of which are incorporated herein by reference in their entireties. This application claims priority to, and the benefit of U.S. The immunogen of claim 17, wherein the NKG2D ligand is MIC. The immunogen of claim 16, wherein the antigen is an NKG2D ligand.ġ8. An immunogen comprising a cell co-expressing BiP and an antigen.ġ7. A method of producing an immunogen comprising contacting a tumor specific antigen with a BiP polypeptide in an amount sufficient to induce partial unfolding of the antigen.ġ6. A method of treating or alleviating a symptom of cancer by administering to a subject an effective amount of a bispecific antibody that specifically binds to MIC and BiP.ġ5. The method of claim 11, wherein the MIC antibody is CM24002.ġ4. The method of claim 9, further comprising administering to said subject a MIC antibody.ġ3. The method of claim 9, wherein the subject has been administered a MIC vaccine.ġ2. A method of treating or alleviating a symptom by administering to a subject a BiP protein or fragment thereof.ġ1. The method of claim 7, wherein the carrier protein is tetnus toxin or diphtheria toxin.ġ0. The method of claim 6, wherein the BiP peptide is conjugated to a carrier protein.ĩ. A method of treating or alleviating a symptom by administering to a subject a BiP peptide in an amount sufficient to induce an anti-BiP immune response.Ĩ. The method of claim 3, wherein the level of soluble MICA or MICB is the level in the serum.ħ. The method of claim 3, wherein the reduction of the level of the soluble MICA or MICBĦ. The method claim 1, wherein the BiP modulator composition reduces the level of soluble MIC in the subject.ĥ. The method of claim 2, further comprising administering an antibody specific for a charperone protein expressed on the surface of a tumor cell.Ĥ. The method of claim 1, wherein the BiP modulating composition is a BiP antibody.ģ. A method of treating or alleviating a symptom of cancer by administering to a subject an effective amount of a BiP modulating composition.Ģ. ![]()
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