Joseph D. Rosenblatt, Seung-Uon Shin and Khaled A. Tolba
Problem
The utility of endostatin is limited due to the fact that the protein has a short half-life. Thus, it needs frequent dosing, and invariably results in low concentration at the site of tumors. If the half-life and stability of anti-cancer targeted drugs like endostatin could be increased, lower concentrations could be used and thus elicit fewer side effects in patients.
Solution
To increase efficacy, the inventors have combined endostatin with the targeting specificity of an anti-tumor antibody by producing antibody-endostatin fusion proteins specific for the HER2/neu tumor antigen.
Competitive Advantage
Improving molecules useful for cancer therapy allow much lower concentration of the toxic chemotherapeutic agents to be used. The advantage of this approach over non-targeted molecules is its stability and the ability to use a lower concentration.
Applications
Constructing chimeric molecules can be applied to a variety of oncologic states depending upon antibody specificity. Various fusion proteins could be created, including ones directed against a variety of known tumor antigens such as EGFR and PSMA in solid tumors and/or CD20 in lymphoma.
Patent Status
United States Patent Application No. US20050008649 A1, entitled "CHIMERIC MOLECULES AND METHODS OF USE," was published on January 13, 2005.
Licensing Opportunity
We are seeking collaborative research and commercial options to further develop this fusion protein for cancer therapy.
About the Inventors
Joseph D. Rosenblatt, M.D., is the William Harrington Professor of Medicine, Microbiology and Immunology and Chief of the Division of Hematology/Oncology in the Department of Medicine at the University of Miami/Miller School of Medicine and also serves in the role of the Associate Director for Clinical and Translational Research of the University of Miami Sylvester Comprehensive Cancer Center. Dr. Rosenblatt is well known in the area of cancer immunotherapy and gene therapy, and has been funded by the National Cancer Institute to pursue development and application of Herpes amplicon vectortechnology for the purpose of immune therapy . Dr. Rosenblatt is an authority on the use of co-stimulatory ligands, and other immune effector molecules delivered through gene transfer and/or antibody fusion proteins for purposes of augmenting immune responses to human and murine tumors.
Dr. Seung-Uon Shin is currently a Research Associate Professor of Clinical Medicine in the Division of Hematology/Oncology at the University of Miami/Miller School of Medicine. He received his Ph.D. in Cell Biology in 1987 from the Albert Einstein College of Medicine and also holds an M.S. in Pharmacy from the Seoul National University. Dr. Shin is a recognized authority in the area of antibody fusion protein production, having performed his postdoctoral research in the laboratory of Dr. Sherrie Morrison, one of the world's premier antibody engineering laboratories. Drs. Rosenblatt and Shin have co-authored numerous articles together on the use of antibody fusion proteins as agents directed against breast and other cancers.
Khaled A. Tolba, M.D. is currently an Assistant Professor of Medicine within the Division of Hematology/Oncology at the University of Miami/Miller School of Medicine. Dr. Tolba trained in the laboratory of Dr. Joseph Rosenblatt and also completed a research fellowship at the Basel Institute of Immunology. Dr. Tolba was a faculty member at the University of Rochester until 2002, when he joined the faculty at the University of Miami Miller School of Medicine. Dr. Tolba is a recognized authority in the area of innate immunity as applied to tumor immunology, as well as in the use of gene therapy, antibody fusion and other modalities to augment immunogenicity of human tumors.
Selected References
Augmentation of anti-tumor responses of adoptively transferred CD8+T cells in the lymphopenic setting by HSV amplicon transduction. Cancer Immunol Immunother. 2008 May;57(5):663-75. Epub 2007 Oct 19. PMID: 17952436
Yi KH, Nechushtan H, Bowers WJ, Walker GR, Zhang Y, Pham DG, Podack ER, Federoff HJ, Tolba KA, Rosenblatt JD.
Adoptively transferred tumor-specific T cells stimulated ex vivo using herpes simplex virus amplicons encoding 4-1BBL persist in the host and show antitumor activity in vivo.
Cancer Res. 2007 Oct 15;67(20):10027-37. PMID: 17942937
Tolba KA, Bowers WJ, Muller J, Housekneckt V, Giuliano RE, Federoff HJ, Rosenblatt JD.
Herpes simplex virus (HSV) amplicon-mediated codelivery of secondary lymphoid tissue chemokine and CD40L results in augmented antitumor activity. Cancer Res. 2002 Nov 15;62(22):6545-51. PMID: 12438249
Tolba KA, Bowers WJ, Eling DJ, Casey AE, Kipps TJ, Federoff HJ, Rosenblatt JD.HSV amplicon-mediated delivery of LIGHT enhances the antigen-presenting capacity of chronic lymphocytic leukemia. Mol Ther. 2002 Oct;6(4):455-63.
Tolba KA, Bowers WJ, Hilchey SP, Halterman MW, Howard DF, Giuliano RE, Federoff HJ, Rosenblatt JD.
Development of herpes simplex virus-1 amplicon-based immunotherapy for chronic lymphocytic leukemia.
Blood. 2001 Jul 15;98(2):287-95.
PMID: 11435295
