Yu Jin-Pu, Li Mu, Ge Wei, Ma Shuang, You Sheng-Guo
Department of Immunology, Oncological Institute and Hospital of Tianjin Medical University, Tianjin 300060, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006 Apr;14(2):351-5.
This study was aimed to investigate the specific anti-L615 leukemia cell immunity induced by L615/DC fused cell vaccine in vivo and in vitro. BM-derived DCs were generated from bone marrow of 615 mice by culturing for 9 - 10 days in culture medium supplemented with GM-CSF and IL-4. Irradiated L615 tumor cells were fused with DC by using PEG to form fused cell vaccine, with which 615 mice were immunized. After immunization, the specific proliferation ability and cytotoxicity against L615 leukemia cells in vitro were examined by MTT and LDH methods. Anti-leukemia effect of fused cell vaccine in vivo was studied by observing the immunotherapy effects on L615 tumor-bearing mice. The results showed that fully mature and functional bone marrow-derived DC were obtained. L615/DC fused cell vaccine could elicit potent specific proliferation response of spleen T cells from immunized mice when contacting with the same antigen at the second time, and could also elicit the effective cytotoxic activity against L615 leukemia cells in vitro, which were significantly different from other groups. In vivo the average survival time of the tumor-bearing mice received immunotherapy with L615/DC fused cell vaccine was 25.7 +/- 1 days, and one fourth of treated tumor-bearing mice survived for long time, but the mice of control group died all, their average of survival time was 17.5 +/- 1 days. The immunized mice survived with no evidence of recurrence when exposed to the second attack of lethal dose of living L615 cells 2 months later. It is concluded that L615/DC fused cell vaccine can improve the immunogenecity of L615 and induce effectively the specific anti-leukemia immunity against L615 leukemia cells to eliminate the residual leukemia cells, prolong the survival time and induce the immune memory to avoid the relapse. Thus, the fused cell vaccine may be an attractive strategy for malignance immunotherapy.
本研究旨在探讨L615/DC融合细胞疫苗在体内外诱导的针对L615白血病细胞的特异性抗免疫反应。通过在添加粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)的培养基中培养9 - 10天,从小鼠骨髓中生成骨髓来源的树突状细胞(DCs)。用聚乙二醇(PEG)将经辐照的L615肿瘤细胞与DC融合,形成融合细胞疫苗,并用其免疫615小鼠。免疫后,采用MTT法和乳酸脱氢酶(LDH)法检测体外针对L615白血病细胞的特异性增殖能力和细胞毒性。通过观察对荷L615肿瘤小鼠的免疫治疗效果,研究融合细胞疫苗在体内的抗白血病作用。结果显示获得了完全成熟且有功能的骨髓来源DC。L615/DC融合细胞疫苗在再次接触相同抗原时,可引发免疫小鼠脾脏T细胞强烈的特异性增殖反应,在体外也可引发针对L615白血病细胞的有效细胞毒性活性,与其他组有显著差异。在体内,接受L615/DC融合细胞疫苗免疫治疗的荷瘤小鼠平均生存时间为25.7±1天,四分之一接受治疗的荷瘤小鼠长期存活,但对照组小鼠全部死亡,其平均生存时间为17.5±1天。2个月后,当免疫小鼠受到致死剂量活L615细胞的第二次攻击时,存活且无复发迹象。结论是L615/DC融合细胞疫苗可提高L615的免疫原性,有效诱导针对L615白血病细胞的特异性抗白血病免疫,以清除残留白血病细胞,延长生存时间并诱导免疫记忆以避免复发。因此,融合细胞疫苗可能是恶性肿瘤免疫治疗的一种有吸引力的策略。