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光动力疗法联合免疫疗法和化学疗法治疗小鼠白血病。

Combination of photodynamic therapy + immunotherapy + chemotherapy in murine leukiemia.

机构信息

Dipartimento di Farmacologia, Università degli Studi, Milano, Italy.

出版信息

Neoplasma. 2010;57(2):184-8. doi: 10.4149/neo_2010_02_184.

DOI:10.4149/neo_2010_02_184
PMID:20099984
Abstract

Photodynamic therapy (PDT) is a treatment for cancer based on the photosensitization of tumor cells by photosensitive drugs and their subsequent destruction on exposure to light of particular wavelength. The combination of drug uptake in malignant tissues and selective delivery of laser-generated light provides an effective therapy with efficient tumor citotoxicity and minimal normal tissue damage. Since immune response of the host is important in the control of tumor growth and spreading, PDT is able to increase the antitumor immunity. In our laboratory we examined the antitumor effect of combination of PDT, with photoactivated M-THPC (meta-tetrahydroxyphenylchlorin, FOSCAN, Temoporphirin), adoptive immunotherapy, with immune lymphocytes, and chemotherapy on advanced murine tumors. Mice bearing L1210 tumor were treated at day +4 with Navelbine (NVB 1mg/Kg), at day +5,+6 with PDT (0.3mg/Kg of mTHPC and 100mW/cm(2) x 200'' of exposure of laser light), and at day + 7 with immune lymphocytes(IL), collected from mice pretreated with PDT(2x10(7) cells). The results show that the combination NVB + PDT + IL demonstrates a significant synergistic antitumor effect while the chemotherapy treatment with low dose of the drug is uneffective. The same positive results were obtained with the combination of Cisplatin (CDDP 0.5mg/Kg), PDT and IL, while the CDDP treatment alone is completely uneffective. In conclusion, these results suggest that it is possible to completely cure animals bearing advanced tumors, with a combined therapy, PDT + adoptive immunotherapy + low dose chemotherapy.

摘要

光动力疗法(PDT)是一种基于光敏药物对肿瘤细胞的光敏化及其随后在特定波长光照射下的破坏的癌症治疗方法。恶性组织中药物的摄取与激光产生的光的选择性传递相结合,提供了一种有效的治疗方法,具有高效的肿瘤细胞毒性和最小的正常组织损伤。由于宿主的免疫反应在控制肿瘤生长和扩散中很重要,PDT 能够增强抗肿瘤免疫。在我们的实验室中,我们检查了 PDT 与光激活 M-THPC(间四羟苯基氯,FOSCAN,替莫泊芬)、过继免疫疗法与免疫淋巴细胞、以及化疗联合治疗晚期鼠肿瘤的抗肿瘤效果。在第 +4 天,用 Navelbine(NVB 1mg/Kg)治疗携带 L1210 肿瘤的小鼠,在第 +5、+6 天用 PDT(0.3mg/Kg 的 mTHPC 和 100mW/cm(2) x 200'' 的激光光暴露)治疗,在第 +7 天用免疫淋巴细胞(IL)治疗,从用 PDT(2x10(7) 个细胞)预处理的小鼠中收集。结果表明,NVB + PDT + IL 联合治疗具有显著的协同抗肿瘤效果,而低剂量药物化疗治疗则无效。同样,Cisplatin(CDDP 0.5mg/Kg)、PDT 和 IL 联合治疗也取得了积极的结果,而单独使用 CDDP 则完全无效。总之,这些结果表明,联合 PDT + 过继免疫疗法 + 低剂量化疗治疗,可以完全治愈患有晚期肿瘤的动物。

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