肿瘤疫苗与白介素-12联合免疫治疗小鼠肉瘤的研究

Therapeutic effects of combination mixed HSP vaccine with interleukin-12 in mice sarcoma

目的:探讨混合热休克蛋白(HSP)/肽与白介素-12(IL-12)和环磷酰胺(CTX)联合治疗小鼠肉瘤的作用及机制。方法:以S-180肉瘤为模型,将瘤组织剪碎,裂解,离心,取上清经Sephacryl S-200层析,截取相对分子质量(50～200)×103段,经SDS-PAGE电泳及Western-blot法鉴定。用提取的HSP/肽免疫小鼠后,再用低剂量CTX及IL-12治疗(强化疫苗),观察无瘤生存率、抑瘤生长率、抑制转移率和存活期。用流式细胞仪,ELISPOT及乳酸脱氢酶等方法检测免疫功能的变化。结果:HSP疫苗与IL-12和CTX联合治疗小鼠S-180肉瘤,80.0%肿瘤完全消退,且100.0%抑制了肺部转移,达长期生存,而对照组全部在40d内死亡。检测表明HSP/肽疫苗形成了免疫预存,从而使IL-12和CTX发挥了抗瘤作用。结论:HSP/肽与IL-12和CTX联合治疗诱发了机体细胞免疫功能,产生强大的抗瘤作用,可能具有临床应用前景。

OBJECTIVE：To investigate the effects of enhanced mixed heat shock protein/peptides for immunotherapy of mouse sarcoma. METHODS： Mixed heat shock protein/peptides were extracted from mouse sarcoma cell line S-180 by chromatography with Saphacryl S-200, identified By SDA-PAGE and Western-blot, and S-180 was transplanted into BALB/C mice, then the mice were immunized by mixed heat shock protein/peptides, then treated with low dose CTX, and IL-12. The tumor regression and long time survival, tumor growth inhibition rates and tumor metastasis were examined. The sub-group of T lymphocyte was examined by FACS and ELISPOT assay. RESULTS： Mice immunized by enhanced vaccine（mixed heat shock protein/peptides/peptides and CTX. IL-12） had the best protected results. The tumor regression and long time survival was 80%. Whereas, all the tumor-hearing controls died within 40 days. CONCLUSION： In this routine tumor model, low dose administration of cyclophophamide and IL-12 can enhance the immunologic and antitumor response to tumor mixed HSP/peptides vaccine, and it has a dramatic anti-tumor effect against S-180 sarcoma. The promising data have raised much hope that it could be a powerful therapeutic agent against tumor.