IMMUNOBIOLOGY OF LAK CELLS

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This proposal will investigate the toxicity and clinical efficacy of autologous IL-2-activated lymphocytes (LAK cells) in patients with advanced malignant disease in a Phase-II clinical trial. The tumoricidal activity of the LAK cell recipients' circulating blood mononuclear cells against natural killer-resistant tumor cell lines, serum levels of IL-2 and IL-2 antibodies and other parameters will be serially monitored. The ability of LAK cells to infiltrate tumors will be determined using 111 Indium-labelled cells and body scans. Serum levels of IL-1, gamma interferon, and tumor necrosis factor will be measured. The in vitro effects of these pyrogenic cytokines on acute phase protein synthesis i cultured hepatoma cells and neuropeptide synthesis in cultured hypothalamus cells will be determined. The effects of these cytokines as well as supernatants from IL-2-activated mononuclear cells and sera from LAK cell recipients on cultured endothelial cells will be investigated. Desialated glycoproteins that appear on the surface of lymphocytes as a consequence of activation by IL-2 will be characterized in two dimensional Western blots using peanut agglutinin and with monoclonal antibodies produced by hybridomas generated from mice immunized with affinity-purified LAK cell proteins. The immunogenicity of these activation antigens in patients receiving LAK cell infusions will be determined with the FACS-IV. This investigation will determine the therapeutic potential and the mechanisms of toxicity of LAK cell treatment as well as provide information on the activation of tumoricidal lymphocytes.