Application of GARP antibodies and fusion proteins in cancer, inflammatory and immune conditions

Description:

Researchers at MUSC have demonstrated that GARP is a novel oncogene due to its cancer-intrinsic roles in promoting invasion and metastasis, as well as its cancer-extrinsic roles in inducing immune tolerance. Administration of a GARP-specific mAb limited metastasis and resulted in an effective cancer therapy in a mouse model of breast cancer (Fig 1). Multiple antibodies and fusion proteins for modulating levels of GARP have been generated and may be useful in treating cancer, acute graft-versus-host disease, transplant rejection, inflammatory conditions and autoimmune diseases. The antibodies can also be used to detect the concentration of GARP in a cancer cell population to determine prognosis.

Overview: GARP (LRRC32) is a docking receptor for TGF-β. Normally only found on the cell surface of regulatory T cells, platelets and other activated leukocytes, GARP is aberrantly expressed on the cell surface of many cancerous cells, including colon cancer, lung cancer, myeloma, as well as prostate cancer. In addition, higher levels of GARP correlate with worse prognosis. As TGF-β controls a diverse set of oncogenic processes and is a master regulator allowing cancer to evade tumor immunity, GARP is believed to be a key regulator in maintaining cell surface TGF-β expression and downstream signaling, thus contributing to oncogenesis. GARP expression appears to be a biomarker for cancer diagnosis and prognosis, and targeting GARP with specific antibodies could be a novel therapeutic platform for cancer by blocking TGF-β availability. In addition, GARP-based antibodies might also be applicable for depleting regulatory T cells and platelets in vivo for boosting immune response and ablating platelet disorders respectively. There are currently no treatment modalities for cancer or autoimmune diseases based on anti-GARP antibodies.

        Aberrant TGF-β expression and/or function are implicated in inflammation, acute graft-versus-host disease, transplant rejection and autoimmune disorders. Modulating GARP with specific antibodies and fusion proteins could be a novel therapeutic platform for inflammatory diseases, acute graft-versus-host disease, transplant rejection and autoimmune disorders.

 

Applications: Reducing expression and/or function of GARP for the treatment and detection of cancers, including colon, lung, myeloma, and prostate cancers. Modulating GARP for treatment of inflammatory and immune disorders.

Advantages:  Reduced metastasis, biomarker for cancer, treatment for cancers, combination immunotherapy, treatment for inflammatory and immune conditions

Key Words: GARP, protein, monoclonal antibody, cancer, inflammatory disease, autoimmune, TGF-β, T cells, tumor, biomarker, immune

 

Publication: Metelli, Alessandra, et al. "Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer." Cancer Research 76.24 (2016): 7106-7117.

 

Inventors: Zihai Li

Patent Status: Two Provisional Applications Filed 3/30/2016 and 9/7/2016

MUSC-FRD Technology ID: P1426 and P1428

 

Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Admin/Archive
MUSC Foundation for Research Development
843-876-1900
 
Inventors:
Zihai Li
Keywords:
cancer
immune
therapeutic
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