Verloes R, Atassi G, Dumont P, Kanarek L
Br J Cancer. 1981 Feb;43(2):201-9. doi: 10.1038/bjc.1981.29.
The experiments aimed at evaluating the optimal parameters in the chemo-immunotherapeutic treatment of the L1210 lymphoid leukaemia grafted to [female BALB/c (H2d) X male DBA/2 (H2d)]F1 hybrid mice, hereafter referred to as CDF1 mice. In vitro irradiation of leukaemic ascites cells by X- or gamma-rays and subsequent inoculation in mice showed that optimum immunogenicity is radiation dose-dependent. Grafting mice with 10(7) leukaemic ascites cells irradiated at optimum dose (80 GyX- or gamma-rays) delays mortality of the animals when challenged later with untreated L1210 cells, but is unable to cure mice. By contrast, specific immunoprophylaxis induced by Micrococcus, complement-triggering polysaccharides or BCG and irradiated leukaemic cells was able to protect mice against grafts of 10(4) L1210 cells. The i.p. route was notably superior to the i.v. route. When mice bearing advanced L1210 tumour were treated by chemotherapy (12 mg/kg of BCNU) on Day 6.5 after grafting 10(4) L1210 cells and subsequently treated by immunotherapy, a very high percentage (up to 90%) of mice with 10(8) leukaemic cells could be cured by repeated 1mg injections of bacterium or polysaccharide, and challenge with irradiated leukaemic cells was unnecessary. Because of the high cure rate obtained, the very regular response pattern and the non-pathogenicity, the bacterium Micrococcus lysodeikticus would seem a promising new candidate for chemo-immunotherapeutic antitumour strategies.
这些实验旨在评估对移植到[雌性BALB/c(H2d)×雄性DBA/2(H2d)]F1杂交小鼠(以下简称CDF1小鼠)体内的L1210淋巴细胞白血病进行化学免疫治疗的最佳参数。用X射线或γ射线对白血病腹水细胞进行体外照射,随后接种到小鼠体内,结果表明最佳免疫原性与辐射剂量有关。用最佳剂量(80 Gy X射线或γ射线)照射的10⁷个白血病腹水细胞移植到小鼠体内,当随后用未处理的L1210细胞攻击时,可延迟动物死亡,但无法治愈小鼠。相比之下,由微球菌、补体触发多糖或卡介苗以及照射过的白血病细胞诱导的特异性免疫预防能够保护小鼠免受10⁴个L1210细胞的移植。腹腔注射途径明显优于静脉注射途径。当在接种10⁴个L1210细胞后第6.5天,对患有晚期L1210肿瘤的小鼠进行化疗(12 mg/kg卡氮芥),随后进行免疫治疗时,通过重复1 mg注射细菌或多糖,高达90%的携带10⁸个白血病细胞的小鼠可以被治愈,且无需用照射过的白血病细胞进行攻击。由于获得了高治愈率、非常规律的反应模式以及无致病性,溶壁微球菌似乎是化学免疫治疗抗肿瘤策略中有前景的新候选物。