CHIMERIC FORM OF TRANSMEMBRANE GLYCOPROTEIN, NKG2D, FOR IMMUNOTHERAPY
Cancer immunotherapy
This construct is useful for immunotherapy for a wide variety of cancers, where the expression of one or more NKG2D ligands is elevated.
The invention relates to the use of a chimeric molecule (e.g., fusion protein) comprising a receptor portion of the transmembrane glycoprotein, NKG2D, and an Fc portion, which binds to one or more NKG2D ligands, to induce cell death in cancers that express elevated levels of NKG2D ligands. A human NKG2D-Fc is commercially available from, for example, R&D Systems, and to date has been used in flow cytometry to detect NKG2D ligands for laboratory studies. We have discovered that such chimera may exert superior immunotherapeutic effects in a wide variety of tumor cell types, as compared to monoclonal antibodies against specific NKG2D ligands, such as MICA.NKG2D-Fc chimeric construct mediates potent and specific complement-dependent lysis, antibody-dependent cellular cytotoxicity, and efficient opsonization of NKG2D ligand-expressing tumor cells. Moreover, this chimera is capable of binding and sequestering any "shed" (e.g., soluble or released) NKG2D ligand(s) produced by tumor cells, thereby alleviating immune suppression due to down-regulation of NKG2D expression in response to tumor-derived soluble ligands. Additionally, the cDNA sequences encoding an NKG2D-Fc fusion polypeptide may be introduced into tumor cells and can function additionally as a vaccine adjuvant.
Inventor: Mizel, Steven B. | Honko, Anna Nichole
Priority Number: US7794731B2
IPC Current: A61K003902 | A61K003800 | A61K003900 | A61K0039116 | A61K003938 | A61K004500 | C07K001400
US Class: 4242341 | 4241841 | 4241901 | 4241921 | 4242031 | 4242421 | 4242821 | 530350 | 530806 | 530825 | 514002
Assignee Applicant: Wake Forest University Health Sciencesnston-Salem
Title: Use of flagellin in the immunotherapy of Yersinia pestis
Usefulness: Use of flagellin in the immunotherapy of Yersinia pestis
Summary: For protecting a mammalian subject (preferably at least 50 years old human) from the effects of Yersinia pestis infection by producing an immune response against Yersinia pestis (claimed).
Novelty: Immunogenic composition for protecting from effects of Yersinia pestis infection by producing immune response comprises flagellin adjuvant; Yersinia pestis antigen and carrier
Biomedical
Pathogen
USA
