Preliminary findings indicate that liposomal tumor necrosis factor (TNF) has potential application as an anti-tumor therapy. In initial studies, it retains cytotoxic activity against cancer cells in culture and yet elicits none of the toxic effects associated with TNF in healthy mice. These studies will be continued and expanded. The goal is to establish the in vivo efficacy of the formulation as a cancer treatment. To this end, liposomal TNF will be produced in sufficient quantity to define (I) its cytotoxic activity against murine B16 melanoma cells, (2) its lethal dose in B57CI/6 mice that bear B 16 melanoma implants, and (3) its in vivo effectiveness as a treatment for murine melanoma. Formulations containing murine and human TNF-alpha will be compared because cross-species variation in TNF-receptor interactions are known. Identically prepared liposomes without TNF-alpha will serve as a control. In light of the tremendous effort that has gone into trying to extend TNF's very narrow therapeutic index, production of an active, clinically acceptable form of TNF would prove to be a major milestone.Awardee's statement of the potential commercial applications of the research: TNF has been shown to possess potent anti-tumor effects against several types of cancer (e. g., melanoma, soft tissue sarcoma and squamous cell carcinoma). However, it also produces severe and often fatal side effects. Use of TNF in liposomal formulation may prevent the toxic side effects, while maintaining or even enhancing TNF's potent anti-tumor properties.National Cancer Institute (NCI)
