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Sunnyvale, CA, United States

Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 117.64K | Year: 2010

DESCRIPTION (provided by applicant): The objective of the proposed research is to characterize a monoclonal antibody (mAb) that binds and blocks Fibroblast Growth Factor 2 (FGF2) for potential use in cancer therapy. The FGF family of growth factors is a large group of factors believed to play a role in the growth of many tumors, as well as in aspects of normal development. In particular, FGF2 (basic FGF) not only stimulates some tumor cells directly, but is a powerful inducer of angiogenesis, the new blood vessel formation needed by tumors to grow. Overexpression of FGF2 and/or correlation of FGF2 level with clinical features or outcome has been reported for melanoma, prostate cancer, pancreatic cancer, liver cancer (hepatoma), esophageal cancer, thyroid carcinoma and other types of cancer. The Applicant has already generated an anti-FGF2 mAb and in preliminary studies shown that it binds a different epitope than other anti-FGF2 mAbs, blocks a bioactivity of FGF2 and, importantly, strongly inhibits growth of a hepatoma tumor xenograft. In the proposed research plan, this anti-FGF2 mAb, designated GAL-F2, will be intensively studied both in vitro and in vivo, in order to provide the scientific justification for moving it toward clinical trials. The ability of GAL-F2 to bind to various forms of FGF2 and to block binding of FGF2 to the four FGF receptors, FGFR1-4, will be determined. The ability of GAL-F2 to inhibit FGF2- induced cell proliferation and migration, and to inhibit soft agar colony formation by human hepatoma cell lines, will be investigated. Another important aim will be to show that GAL-F2 has potent anti-angiogenic properties, for example by showing that the mAb inhibits blood vessel formation induced by xenografts of a highly angiogenic retinoblastoma cell line. Finally, experiments will be conducted to investigate the capability of the GAL-F2 mAb to block growth of human hepatoma tumor xenografts in mouse models; the results will be critical for the potential choice of hepatocellular carcinoma as the initial clinical indication for the mAb. It is expected that in Phase II of this grant proposal, more extensive animal model and mechanism of action studies will be conducted, and the GAL-F2 mAb will be converted into a humanized antibody suitable for clinical development. PUBLIC HEALTH RELEVANCE: Despite recent scientific advances, cancer remains a major medical problem. The objective of the planned program is to study a monoclonal antibody that targets a growth factor believed to be involved in many tumors. The antibody has the potential to be an effective drug for various types of cancer including liver, pancreatic, and prostate.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 957.30K | Year: 2011

DESCRIPTION (provided by applicant): The objective of the proposed research is to thoroughly characterize a humanized monoclonal antibody (mAb) that binds and inhibits human Fibroblast Growth Factor 2 (FGF2; basic FGF) for potential use in cancer therapy.FGF2 can directly stimulate tumor cell proliferation and also induces migration, proliferation and differentiation of endothelial cells, so is a potent angiogenic factor. FGF2 is strongly expressed in most gliomas and in renal cell cancer (RCC), contributes to progression of prostate tumors, and is a factor for the growth of melanomas, but has been most strongly associated with hepatocellular carcinoma (HCC), the predominant form of liver cancer (hepatoma). The Applicant has generated an anti-FGF2 mAb, GAL-F2, and shown that it neutralizes all tested biological activities of FGF2 and, importantly, strongly inhibits the growth of tumor xenografts from three different HCC cell lines. The GAL-F2 mAb has already been humanized to generate HuGAL-F2, a mAb potentially suitable for administration to human patients. Hence, the overall goal of the proposed research plan is to generate a data package of functional assay results, mechanism of action findings, animal model studies and initial safety studies that will support filing of an IND for this humanized mAb. More specifically, the binding affinity of HuGAL-F2 for human and mouse FGF2 will be precisely determined, and assays will be conducted for HuGAL-F2 inhibition of (i) binding of FGF2 to its cellular receptorsFGFR1-4, (ii) FGF2-induced phosphorylation and cell proliferation, and (iii) FGF2-induced angiogenesis. The ability of HuGAL-F2 to inhibit growth of xenografts from several HCC and RCC cell lines will be explored extensively. In these studies, HuGAL-F2 will be tested both as a single agent and in combination with other drugs: Nexavar, approved for treatment of HCC and RCC; Sutent, approved for treatment of RCC; and Avastin, currently in clinical trials for HCC. The mechanism of action of HuGAL-F2 against tumor growth will be investigated by measuring cellular proliferation, angiogenesis and apoptosis in xenografts from mice treated with the mAb. To expand the potential indications for HuGAL-F2 to brain cancer, the effectiveness of this mAb in treating orthotopic xenografts generated from glioblastoma (GBM) stem cells will also be investigated, as such xenografts replicate the characteristics of true clinical GBMs with high fidelity. Finally, to advance the humanized mAb toward an IND for clinical trials and to help attract a corporate partner/licensee to sponsor further development, a standard tissue cross-reactivity study and an initial toxicology study in rodents will be performed. PUBLIC HEALTH RELEVANCE: Despite recent scientific advances, cancer remains a major medical problem. The objective of the planned program is to test a monoclonal antibody that targets a growth factor believed to be involved in many tumors. The antibody will have the potential to be an effective drug for various types of cancer including liver, kidney, and brain.


Patent
Galaxy Biotech, Llc | Date: 2011-10-28

The present invention is directed toward a monoclonal antibody to fibroblast growth factor receptor 2, a pharmaceutical composition comprising same, and methods of treatment comprising administering such a pharmaceutical composition to a patient.


Patent
Galaxy Biotech, Llc | Date: 2013-03-06

The present invention provides a bispecific antibody having a binding domain that binds to FGF2, a pharmaceutical composition comprising same, and methods of treatment comprising administering such a pharmaceutical composition to a patient.


Patent
Galaxy Biotech, Llc, Kennedy Krieger Institute and Johns Hopkins University | Date: 2010-01-19

The application is directed toward a method of treating a brain tumor in a patient comprising systemically administering a monoclonal antibody.

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