This is an application for a Phase I contract in which we will evaluate the feasibility of using a new cancer treatment regimen in humans. The overall goal of this Phase I study will be to determine the toxicity and antitumor activity of this new regimen in rabbits. The information derived from the Phase I experiments in animals will provide the basis for a Phase II study of this regimen in human patients with lung cancer.The treatment regimen which we will evaluate is a two-step process: 1. Activation of systemic macrophages by intravenous inoculation of an effective macrophage activator such as BCG; 2. Release of antitumor factors from the activated macrophages triggered by intravenous inoculation of detoxified endotoxin (monophosphoryl lipid A, henceforth abbreviated DE).Toxicity will be assessed by measuring physical, hemodynamic, hematological, chemical, and histological changes in rabbits after treatment. Antitumor activity will be assessed by monitoring post-treatment serum for antitumor activity against murine and human cancer cell lines.The hypothesis which will be tested is that treatment with BCG followed by DE is a regimen which elicits the production of soluble endogenous factors which have significant antitumor activity without exposing the host to unacceptable toxicity.Successful research and development of this new treatment regimen for use against human cancer will allow us to work with a manufacturing company in making this new regimen commercially available.National Cancer Institute (NCI)
