Treatment of Human Solid Malignancies with Autologous Activated Lymphocytes and Cimetidine: A Phase II Trial of the Cancer Biotherapy Research Group

Objective: The Cancer Biotherapy Research Group conducted a clinical trial to verify encouraging reports of antitumor activity of autolymphocyte therapy. Patients and Methods: Patients with a variety of advanced solid malignancies underwent an initial leukapheresis procedure to collect about 5 × 109 autologous lymphocytes that were stimulated in vitro for 3 days with anti-CD3 monoclonal antibody in the presence of indomethicin and cis-retinoic acid to obtain media that was frozen in aliquots. This media contained significant amounts of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon-γ, and IL6, but no IL-2. Subsequently patients underwent up to 6 monthly leukaphereses to collect 2-5 × 109 autologous lymphocytes that were incubated in vitro for 6 days in the cryopreserved media containing autologous lymphokines, resulting in a cell population enriched for noncytotoxic T-helper lymphocytes. These were administered intravenously monthly for up to 6 months with daily oral cimetidine at a dose o...