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Government-Owned Inventions; Availability for Licensing: Natural Killer Cells in Xenotransplantation and Establishment of a Target Cell Line Producing Porcine Endogenous Retrovirus

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AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

SUMMARY:

The invention described below is owned by an agency of the U.S. Government and is available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development.

ADDRESSES:

Licensing information for the technology described below may be obtained by contacting John Rambosek, Ph.D., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7056 ext. 270; fax: 301/402-0220; e-mail: rambosej@od.nih.gov.

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SUPPLEMENTARY INFORMATION:

The worldwide shortage of human organs and tissues for allotransplantation combined with recent advances in transplantation immunobiology, surgery and medicine, have sparked renewed interest in the clinical use of xenotransplantation, the use of living nonhuman animal materials for the treatment of human diseases. In addition to whole organ transplants, cellular implants and ex vivo use of living material from animal sources have been suggested for treatment of disease in human patients. For a variety of reasons, the pig is currently the source animal of choice for xenotransplantation in humans, but there are two major obstacles to successful pig to human xenotransplantation. These are the immune response, responsible for rejecting xenotransplants, and the risk of transmission of infection including porcine endogenous retrovirus, which, at least at the present time, cannot be removed from the xenotransplantation porcine source. Natural killer (NK) cells play an important role in the delayed rejection of xenotransplants, and have been shown to infiltrate rejecting grafts.

Current efforts in the Laboratory of Immunology and Virology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Start Printed Page 36291FDA, are aimed at understanding the human NK cell response to porcine target cells. Findings suggest that NK cells have the capacity to participate in early stages (hyperacute or acute rejection) of xenograft rejection as well as later stages (delayed rejection). In addition, human NK cell activity against porcine cells as measured by lysis and proliferation, is regulated by certain cytokines such as interleukin (IL)-2, IL-12, and IL-15, but not by IL-18 and IL-8. Moreover, the human NK cell response to porcine endothelial cells is regulated by the combination of redox status and nitric oxide (NO) availability, such that under conditions of oxidative stress, lysis of porcine endothelial cells is inhibited by NO through a nuclear factor-kappa B-dependent pathway. Finally, in the process of carrying out these investigations, a new porcine cell line, MS-PBMC-J2 (J2), was established from the peripheral blood of a NIH miniswine. J2 constitutively produces infectious porcine endogenous retrovirus. J2 expresses porcine CD2, CD8, CD16, CD31, and MHC class I and class II but does not express CD3 or CD4. Phenotypically it resembles NK cells, but does not mediate NK-like activity. Further studies into the regulation of human NK cell anti-porcine cytotoxicity are underway, and other experiments using J2 as a model of PERV production are planned.

The cell line (our reference no. E-046-01/0) is available for licensing under a Biological Materials License Agreement. The scientists may also be interested in collaborative arrangements for the further research and development of this technology.

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Dated: June 29, 2001.

Jack Spiegel,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.

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[FR Doc. 01-17289 Filed 7-10-01; 8:45 am]

BILLING CODE 4140-01-P