[Federal Register Volume 66, Number 133 (Wednesday, July 11, 2001)]
[Notices]
[Pages 36290-36291]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-17289]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


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

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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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: [email protected].

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,

[[Page 36291]]

FDA, 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.

    Dated: June 29, 2001.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 01-17289 Filed 7-10-01; 8:45 am]
BILLING CODE 4140-01-P