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.
• Treating cancer patients using adoptive immunotherapy
• Applicable to treating infectious disease that can benefit from increased expression of cytokine
Transformed T lymphocytes cultures can express cytokines and specific TCRs
Steven Rosenberg (NCI) , Richard Morgan (NCI), Cary Hsu (NCI)
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