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Adoptive Immunotherapy with T Lymphocytes Engineered for Enhanced Survival

Summary
Researchers at the NCI have developed a method of genetically engineering lymphocytes to expressed elevated levels of cytokine proteins. This technology is useful for improving cellular adoptive immunotherapies to treat a range of infectious diseases and cancers.
NIH Reference Number
E-340-2004
Product Type
Keywords
  • ACT, T-cells, immunotherapy, cytokines, TCR
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

Adoptive immunotherapy has repeatedly been shown to be useful in the treatment of patients with metastatic melanoma. However, clinical efficacy of this treatment is limited by the short-lived survival of the transferred, autologous, antigen-specific T cells. It would be desirable to genetically modify effector cells to provide not only enhanced effector cell survival, but also desired antigen specificity, and improved function, and safety. The current technology provides a method address this desire, by genetically modifying lymphocytes using retroviral vectors.

Specifically, isolated autologous T lymphocytes can be transformed with polynucleotides encoding endogenous cytokines, for example IL-7 or IL-15. IL-15-transduced lymphocyte cultures demonstrate prolonged in vitro persistence. In addition, T cells can be transduced to express not only cytokines but also T cell receptors to confer specificity for certain antigens. Recent data showed that human T lymphocytes engineered to express a murine anti-human p53 T cell receptor can recognize tumor cell lines, as well as fresh human tumors, and are able to kill p53-expressing human tumor cells.

Also provided in the invention are methods for treating patients with transformed lymphocytes as part of adoptive immunotherapy. Applications of this technology beyond cancer include the potential use of cytokine expressing cells in treating infectious and autoimmune diseases and vaccination.

Potential Commercial Applications

• Treating cancer patients using adoptive immunotherapy
• Applicable to treating infectious disease that can benefit from increased expression of cytokine

Competitive Advantages

Transformed T lymphocytes cultures can express cytokines and specific TCRs

Inventor(s)

Steven Rosenberg (NCI) , Richard Morgan (NCI), Cary Hsu (NCI)

Development Stage
Publications

Gattinoni L, et al. PMID 16203864
Wang LX, et al. PMID 16288050
Gattinoni L, et al. PMID 16622476
Cohen CJ, et al. PMID 16237072
Hsu C, et al. PMID 16301627
Rosenberg SA, Dudley ME. PMID 15381769
Klebanoff CA, et al. PMID 14762166
Liu K, Rosenberg SA. PMID 12806273
Liu K, Rosenberg SA. PMID 11714800

Patent Status
  • U.S. Patent Issued: U.S. Patent Number
  • Foreign Issued: - Patent Number
Therapeutic Area
Posted
Wednesday, October 11, 2017