Analysis of the immune response of tumor-bearing host at the immunochemotherapy -from the viewpoint of optimum combination of chemotherapy and immunotherapy -

免疫化疗时荷瘤宿主的免疫反应分析-从化疗与免疫治疗最佳组合的角度-

基本信息

批准号：
12671212
负责人：
FUJIMOTO Toshihiro
金额：
$ 2.11万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671212/
关键词：
Irinotecan(CPT-11)OK-432 Th1 IL-12 immunochemotherapy tumor bearing state immunochemc therapy

项目摘要

Chemotherapy with lower dose of irinotecan (CPT-ll) exerts larger antitumor effect. In this study, SN-38, the active metabolite of CPT-ll, exerted dose-dependent inhibition of interferon (IFN)-γ and interleukin (IL)-10 production induced by streptococcal preparation OK-432 in mouse splenocytes. In contrast, the optimum concentration of SN-38 (0.4-0.8(μg/ml) increased IL-6 and IL-12 production by OK-432 activated macrophages. In tumor-bearing mice (C57BL/6 mice bearing with B16 melanoma), CPT-11 inhibited tumor growth and OK-432 had an additive antitumor effect with CPT-11. Investigation of cytokine production showed that CPT-11 treatment principally inhibited IL-12 and IFN-γ production, which was improved by the combined administration with OK-432. These results indicate that CPT-11 inhibits type-1 T helper (Th1) cells despite its potential to stimulate macrophages and that OK-432 enhances the antitumor activity of CPT-11 by increasing Th1-cytokine production (Anticancer Research 21 : 2505-2510, 2001).In the treatment for the peritoneal metastasis of gastric carcinoma, we may control disseminated cancer cells by intraperitoneal immunochemotherapy using MMC and OK432 in patients with curative resection (Oncology, 2002, in press).Briefly, these results have demonstrated the efficacy of the combination of chemotherapy and immunotherapy.

化学疗法较低剂量的伊立替康（CPT-LL）导出较大的抗肿瘤作用。在这项研究中，CPT-LL的活性代谢产物SN-38施加了剂量依赖性抑制干扰素（IFN）-γ和白介素（IL）-10 -10链球菌制剂诱导的产生OK-432在小鼠脾脏中诱导的。相反，OK-432活化的巨噬细胞的SN-38（0.4-0.8（0.4-0.8（0.4-0.8（μg/mL））的最佳浓度增加了IL-6和IL-12的产生。在肿瘤的小鼠中（C57BL/6小鼠在B16黑色素瘤中轴承的C57BL/6小鼠），CPT-11轴承CPT-11抑制了CYOR TUMOR的生长和CY1的研究。 showed that CPT-11 treatment principally inhibited IL-12 and IFN-γ production, which was improved by the combined administration with OK-432. These results indicate that CPT-11 inhibits type-1 T helper (Th1) cells despite its potential to stimulate macrophages and that OK-432 enhances the antitumor activity of CPT-11 by increasing Th1-cytokine production (Anticer Research 21: 2505-2510, 2001年）。在胃癌的腹膜腹膜转移治疗中，我们可以通过腹膜内免疫化学疗法使用MMC和OK432在治疗切除术的患者中控制传播的癌细胞（Briefly，这些结果，这些结果都证明了化学疗法和免疫疗法的效率。