The Phase I objective of this proposal is to assess the potential for antitumor effects of a novel alpha interferon (IFNalpha), ovine trophoblast protein-1 (oTP-1), as well as its activity against human and feline immunodeficiency virus (HIV, FIV) infections. Several characteristics of OTP-1 merit its investigation as an antitumor agent and potentially therapeutic for human and feline AIDS. OTP-1 is as potent an antiviral agent as any known IFN, and importantly, displays anticellular activity in the absence of toxicity. It acts on human cells both in antiviral assays and in inhibition of HIV reverse transcriptase activity. OTP-1 is available in both """"""""natural"""""""" and recombinant forms in large quantities, and the functionally important portions of the molecule have been localized allowing for the development of agonists and antagonists. We will employ the following specific aims: (1) determine the antineoplastic activity of OTP-1 in vitro against a panel of tumor cell lines, (2) examine the antiviral activity of OTP-1 and OTP-1 peptides relative to other IFNs in HIV and FIV infection, (3) increase the therapeutic potential of OTP-1 by examining recombinant OTP-1 and human IFNalpha chimeras and construction of OTP-1 mutants with enhanced activity against tumor cells and HIV and FIV infections. Since IFNalphas have been shown to be effective antitumor agents in clinical trials and OTP-1 has demonstrated potent anticellular activity without toxicity, we anticipate that OTP-1 will prove to be an invaluable tool in antitumor therapy.
