SBIR-STTR Award

Adoptive immunotherapy has provided an additional method of treating cancer. The use of Lymphokine Activated Killer (LAK) cells and in conjunction with interleukin-2 have shown remarkable results in some terminal cancer patients. Recently IFN-A has been shown to have a synergistic effect in animal TIL models. To further enhance TIL therapy, we suggest retroviral mediated gene transfer of human IFN-a2 into TIL cells. INF-a2 and IFN-A AID (BGIII) will be cloned into a retroviral transduced TIL cells expressing IFN will be assayed for efficacy and safety. IFN-a2 is being used for future clinical work while IFN-a2 A/D will be used for murine models. The transduced TIL cells will be examined for IFN production, changes in growth properties, cytotoxicity against tumor and non-tumor cell lines, surface marker phenotype, and production of other relevant cytokines.Awardee's statement of the potential commercial applications of the research:Adoptive immunotherapy is becoming established as the fourth major modality for cancer treatment. Augmentation of TIL therapy by gene transfer to deliver cytokines such as a interferon to tumor sites could lead to major new cancer treatments. This would require the provision of safe approved retroviral vectors, and also perhaps, the provision of the @ces of transducing the TIL cells from patients, and their amplification and characterization.National Cancer Institute (NCI)

Adoptive immunotherapy has proven useful to treat human melanoma. The use of lymphokine activated killer cells and tumor infiltrating lymphocytes in conjunction with IL-2 have produced significant results in some terminal cancer patients. Recently, interferon alpha has been shown to have a synergistic effect with IL-2/TIL in animal TIL models. To further enhance TIL therapy, a Phase I study (Section D) involved constructing retroviral vectors to express alpha-IFN in human TIL cells. The Phase II study will optimize the expression of IFN alpha in TIL cells, and in tumor cells themselves. These vectors will be studied in rodent models, and compared with another interferon vector, IFN gamma, that has independently been constructed at GTI. It is of interest to compare these two interferons, since IFN alpha is known to up-regulate class I MHC while IFN gamma up-regulates MHC class I and II. After suitable preclinical and safety studies, a clinical protocol to treat malignant melanoma and possibly other cancer patients is proposed to be prepared by our clinical collaborators at the NIH, and after RAC and FDA approval of such physician-sponsored protocols, a clinical study will be conducted at the NIH. The GTI group will provide clinically certified retroviral vectors for this clinical study.

Thesaurus Terms:
cytotoxic T lymphocyte, interferon alpha, method development, neoplasm /cancer immunology, neoplasm /cancer immunotherapy, transfection gene expression, gene therapy, interleukin 2, neoplasm /cancer vaccine, oligonucleotide, phenotype, transfection vector, tumor necrosis factor alpha Retroviridae, enzyme linked immunosorbent assay, laboratory mouse, microorganism culture, molecular cloning, tissue /cell culture, western blotting