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ID# UMF-10

Perforin-2 in Macrophages for Anti-bacterial Therapy

Drs. Vadim Deyev and Eckhard R. Podack

Problem

The incidences of serious bacterial infections are increasing at home and in hospitals due to the development of antibiotic resistance. Furthermore there are certain bacteria such as those causing tuberculosis that are naturally resistant to most antibiotics. There is an urgent need to discover novel antibacterial agents.

Solution

This invention describes a recently discovered, Perforin 2, that is produced by phagocytes as a defense against infection. Until its discovery at the University of Miami, it was not known that Perforin 2 can kill bacteria and other infectious cells by drilling large holes into their membranes. The synthesis of Perforin 2 by phagocytes is under careful and complex control in order to avoid overproduction of a protein that could potentially damage the body’s own cells. Harnessing the power and augmenting the levels of Perforin 2 could be not only a powerful anti-infective agent but also a potential immunomodulator.

Competitive Advantage

This is a unique antibacterial approach in that it will not lose efficacy due to the development of resistance.

Applications

This invention will develop and test new small molecules that can augment Perforin 2 synthesis in phagocytes at the time of infection. It is expected that Perforin 2 will kill bacteria that are resistant to antibiotics because the killing mechanism relies on physical destruction of bacteria rather than on interference with their metabolism. Some of the uses for Perforin 2 include:
- Drug resistant bacterial infections
- Tuberculosis
- Leprosy
- Vancomycin resistant Staphylococcus
- Combination with standard antibiotics

Patent Status

International Patent Appln No. PCT/US2007/70259 entitled “PERFORIN 2 PROTEINS” was filed on June 1, 2007.

Licensing Opportunity

About the Inventors

Vadim Deyev, M.D., Ph.D.
Vadim Deyev, M.D., Ph.D., is an Assistant Scientist at the Department of Microbiology and Immunology. Dr. Deyev is currently working along with Dr. Podack to develop and utilize an antibody that effectively halts inflammation in mouse models of asthma. Dr. Deyev’s project, one of the first of five research projects chosen from a number of applicants, will be conducted in the newly opened labs at the Wallace H. Coulter Center for Translational Research at the University of Miami. Eckhard R. Podack, M.D., Ph.D.
Eckhard R. Podack, M.D., Ph.D. is the University of Miami/Miller School of Medicine Chair of the Department of Microbiology and Immunology. From 1996-2006, he was also the Associate Director for Basic Science at the University of Miami/Sylvester Comprehensive Cancer Center. Dr. Podack received his M.D. in 1968 from Johann Wolfgang Goethe University, Frankfurt, Germany; Medical Board. Some of his research interests include: induction of immunity by heat shock protein gp96-Ig, immunotherapy for advanced non-small-cell lung carcinoma (NSCLC), and CD30, the governor of T-cells.

Selected References

Blazar BR, Levy RB, Mak TW, Panoskaltsis-Mortari A, Muta H, Jones M, Roskos M, Serody JS, Yagita H, Podack ER, and Taylor PA. CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease. J Immunol. 2004;173:2933-2941. Raez LE, Cassileth PA, Schlesselman JJ, Sridhar K, Padmanabhan S, Fisher EZ, Baldie PA, and Podack ER. Allogeneic vaccination with a B7.1 HLA-A gene-modified adeno-carcinoma cell line in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2004;22:2800-2807. Marks L, Altman NH, Podack ER, and Levy RB. Donor T cells lacking Fas ligand and perforin retain the capacity to induce severe GvHD in minor histocompatibility antigen mismatched bone-marrow transplantation recipients. Transplantation. 2004;77:804-812. Raez LE, Cassileth PA, Schlesselman JJ, Padmanabhan S, Fisher EZ, Baldie PA, Sridhar K, and Podack ER. Induction of CD8 T-cell-Ifn-gamma response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma. Cancer Gene Ther. 2003;10:850-858.

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