IMMUNOBIOLOGY OF LAK CELLS

LAK 细胞的免疫生物学

• 批准号: 3186450
• 负责人: JAMES W MIER
• 金额: $ 24.46万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-02-01 至 1990-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3186450
• 关键词: antibody dependent killer cell; cell bank /registry; cell migration; cytokine; eosinophil; genetic manipulation; glycoproteins; hepatocellular carcinoma; human subject; human therapy evaluation; immunosuppression; interferons; interleukin 2; laboratory mouse; laboratory rabbit; lymphokines; monoclonal antibody; monocyte; neoplasm /cancer immunotherapy; neuropeptides; peripheral blood vessel; radiotracer

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.

本研究拟探讨其毒性及临床疗效