Retroviral Vectors for Selective Reversible Immortalization of Stimulus-responding Primary Cells

Description of Invention:
Researchers at the National Cancer Institute-Frederick, NIH, have developed a novel set of retroviral vectors and producer cell lines useful for selective reversible immortalization of primary cells (i.e. lymphocytes) that respond to a stimulus, such as a viral antigen (e.g. HIV toxoids), a tumor antigen, or a growth factor.

Derived from the murine leukemia virus (MuLV), these retroviral vectors will only infect dividing cells. Therefore, only primary cells activated by the stimulus will be infected and immortalized, thereby creating an "antigen-specific trap."

The primary cells to be immortalized can be in targeted tissue or in stimulated ex vivo culture. The transduced cells can be expanded to large numbers without differentiating, and returned to the primary cell stage by removal of the introduced genes using a vector excision strategy.

Applications:

• Isolation/ replication of normally short-lived primary cells that respond to a stimulus
• Immortalization of antigen-specific T cells for vaccine development or adoptive transfer immunotherapy
• Production of primary cell lines for large-scale production of cell-secreted factors, cytokines, and other molecules

Advantages:

• System acts as an anti-senescence treatment: cells that are normally short-lived can be kept in culture for years
• Vectors with different markers are available to identify transduced cells and for cell selection
• Excision allows for gene/marker removal
• The MuLV-based system only infects dividing (e.g. activated) cells

Inventors:
Eugene V Barsov (NCI)
David E Ott (NCI)


Patent Status:
HHS, Reference No. E-140-2010/0

Research Tool -- patent protection is not being pursued for this technology

Relevant Publication:

1. E Barsov et al. Capture of antigen-specific T lymphocytes from human blood by selective immortalization to establish long-term T-cell lines maintaining primary cell characteristics. Immunol Lett. 2006 May 15;105(1):26-37. [ PubMed: 16442639 ]
2. H Andersen et al. Transduction with human telomerase reverse transcriptase immortalizes a rhesus macaque CD8+ T cell clone with maintenance of surface marker phenotype and function. AIDS Res Hum Retroviruses 2007 Mar;23(3):456-465. [ PubMed: 17411379 ]

Licensing Status:
Available for biological materials licensing only.

Collaborative Research Opportunity:
The Center for Cancer Research, AIDS and Cancer Virus Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Portfolios:
Devices/Instrumentation
Devices/Instrumentation - Research Tools and Materials
Cancer
Cancer - Research Materials
Infectious Diseases
Infectious Diseases - Research Materials



For Additional Information Please Contact:
Patrick McCue Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: McCuepat@mail.nih.gov
Phone: 301-496-7057
Fax: 301-402-0220


Ref No: 2106

Updated: 06/2010