A STUDY ON IMMUNOTHERAPY OF ORAL CANCERS

比较口腔癌复发与未复发患者外周血淋巴细胞、CD3~+、CD_4~+、CD_8~+、CD_4/CD_8比值等细胞免疫功能。肿瘤复发组细胞免疫功能明显下降。然后，对31例接受OK-432免疫治疗的口腔癌患者进行了检测，并与23例未接受免疫治疗的对照组患者进行了比较。OK-432免疫治疗可抑制肿瘤治疗所致的CD3~+细胞和CD_4~+细胞的下降，对肿瘤治疗过程中NK细胞活性的下降也有抑制作用。本研究不仅观察了OK-432等单一化疗药物对口腔癌患者的治疗效果，还观察了自体LAK细胞过继转移联合抗CD3单抗激活的重组白介素2(RIL-2)过继免疫治疗口腔癌的疗效。尽管细胞毒活性…为提高CD3/LAK细胞过继免疫治疗的疗效，探讨了CD3/LAK细胞过继免疫治疗与化疗或其他细胞因子联合应用的效果。用CDDP、5-FU等化疗药物对口腔癌细胞建立的靶细胞株进行预处理，可提高CD3/LAK细胞的细胞毒活性。相反，靶细胞经干扰素-γ、肿瘤坏死因子-α处理后，CD3/LAK细胞的细胞毒活性降低。目前的免疫学研究表明，T细胞表面的CD28和APC上的CD80、CD86等共刺激信号和T细胞表面的CD28、CD80、CD86等共刺激信号是诱导、激活和克隆性扩增初始T细胞为活性CTL所必需的。虽然活性B细胞、巨噬细胞和专业APC如树突状细胞表达CD80和CD86，但几乎所有肿瘤细胞都不表达CD80和CD86。CD80基因转染CD80阴性小鼠纤维肉瘤细胞系(Meth A)的实验动物模型显示，同系小鼠对Meth A的生长有排斥反应。Meth A特异性排斥反应的免疫学特异性表明，该基因治疗可诱导肿瘤特异性CTL。较少

Cell-mediated immunity of oral cancer patients in terms of peripheral blood lymphocytes, CD3^+, CD4^+, CD8^+, CD4/CD8 ratio, and so on were compared between patients with tumor recurrence and patients without recurrence. Tumor recurrence group showed significant decrease in cell-mediate immunity. Then, Thirty-one oral cancer patients who received immunotherapy by OK-432 were examined and compared with 23 control patients who received no immunotherapy. Decrease of CD3^+ cells and CD4^+ cells due to cancer treatments was inhibited by OK-432 immuno-therapy, and inhibitory effect on decrease of NK activity during cancer treatments was also recognized in the immunotherapy group. Not only single BRM therapy such as OK-432 but also the therapeutic efficacy of adoptive immunotherapy with the adoptive transfer of autologous LAK cells plus recombinant interleukin-2 (rlL-2) activated with anti-CD3 monoclonal antibody and rlL-2 was investigated in oral cancer patients. Although cytotoxic activity … More of single CD3/LAK cells induced by solid phase anti-CD3 monoclonal antibody plus rlL-2 showed lower than that of LAK cells activated by single rlL-2, total lytic activity of whole culture of CD3/LAK cells showed greater because of vigorous proliferation of CD3/LAK cells.To improve the therapeutic efficacy of adoptive immunotherapy by CD3/LAK cells, the effect of the combination therapy of CD3/LAK and chemo-therapy or administration of other cytokines was investigated. Pretreatments of target cultured cell lines established from oral cancer cells with chemotherapeutic agents such as CDDP,5-FU increased cytotoxic activity of CD3/LAK cells. In contrast, pretreatments of the target cells with IFN-gamma, TNF-alpha decreased the cytotoxic activity of CD3/LAK cells. By combination of pretreatment of IFN-gamma and CDDP or 5-FU the decrease of the cytotoxic activity of CD3/LAK cells by IFN-gamma was reduced in resulting compensation of the cytotoxic activity.Recent immunological studies have revealed that both specific ligand and co-stimulatory signals such as CD28 on T cells and CD80, CD86 on APC are required for the induction, activation and clonal expansion from naive T cells to active CTL.Although active B cells, macrophages, and professional APC such as dendolitic cells were expressing CD80, CD86, almost all tumor cells showed no expression of them. The experimental animal model of CD80 gene transfection to CD80 negative mice fibrosarcoma cell line (Meth A) showed rejection of growth of Meth A in syngenic mice. The immunologic specificity of Meth A specific rejection indicted that tumor specific CTL is induced by this gene therapy. Less