IMMUNOBIOLOGY OF LAK CELLS

该提案将研究阿司匹林的毒性和临床疗效。 患者自体IL-2激活的淋巴细胞(LAK细胞) 晚期恶性疾病正在进行二期临床试验。这个 LAK细胞受者外周血的杀瘤活性 单个核细胞对抗自然杀伤分子耐药肿瘤细胞系， 血清IL-2和IL-2抗体水平及其他参数将 被连续监测。LAK细胞的侵袭能力 肿瘤将使用111个铟标记的细胞和 身体扫描。血清IL-1、γ-干扰素水平与肿瘤 将测定坏死因子。这些化合物的体外作用 致热细胞因子对急性时相蛋白合成的影响 培养的肝癌细胞与神经肽合成 将对下丘脑细胞进行测定。这些因素的影响 IL-2激活的细胞因子及上清液 LAK细胞受者单个核细胞和血清对体外培养的影响 将对血管内皮细胞进行研究。去唾液酸糖蛋白 它们出现在淋巴细胞表面，这是 IL-2的激活将在两个维度上表征 用花生凝集素和单抗进行免疫印迹 小鼠产生的杂交瘤产生的抗体 用亲和纯化的LAK细胞蛋白免疫。这个 这些激活抗原在受试者体内的免疫原性 LAK细胞输注将用FACS-IV确定。这 调查将确定治疗潜力和 LAK细胞治疗的毒性机制及提供 关于杀瘤淋巴细胞激活的信息。

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.