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用“肿瘤免疫”RNA或纤维蛋白片段E抗体进行免疫治疗使豚鼠肝癌完全消退。

Complete regression of a guinea pig hepatocarcinoma by immunotherapy with "tumor-immune" RNA or antibody to fibrin fragment E.

作者信息

Schlager S I, Dray S

出版信息

Isr J Med Sci. 1976 Apr-May;12(4-5):344-59.

PMID:181352
Abstract

Two novel immunotherapeutic regimens were developed for a uniformly lethal, intradermally growing transplantable ascites variant (line 10) of a diethylnitrosamine-induced hepatoma in strain 2 guinea pigs. In an apparently tumor-specific immunotherapy model, 32 guinea pigs were cured by the injection into the tumor area, five or seven days after tumor challenge, of syngeneic or xenogeneic RNA extracts obtained from lymphoid tissues of line 10-immune strain 2 guinea pigs or rhesus monkeys, as part of a total regimen which included syngeneic nonsensitive peritoneal exudate cells injected prior to, and tumor-specific antigen injected after, the RNA. In another immunotherapy model, not tumor-specific, 18 strain 2 guinea pigs were cured by the injection into the tumor area, 6 and 16 days after tumor challenge, of antibody specific for fibrin fragment E (FFE), an essential component in the formation of a fibrin matrix considered to be important in tumor development. When therapy was delayed to 12 days in the RNA test system, or to 16 days in the anti-FFE test system, complete abrogation of the tumors did not occur. The long-term survival of the 50 successfully treated animals and their immunity to further tumor challenge indicated that both immunotherapeutic procedures had systemic effects. To test this further, line 10 cells were injected intradermally simultaneously at two sites and only one site was treated. When the one tumor location was treated with anti-FFE, complete regression of the treated tumor and a 30% retardation in the development of the untreated tumor were observed. When this tumor location was treated with the RNA regimen, complete regression of the tumors occurred at both the treated and the untreated sites. Optimal conditions for both immunotherapeutic models and their combination have yet to be establshed. Nonetheless, both immunotherapeutic regimens were more effective than any other immunotherapy thus far reported for this tumor, including the use of BCG or its derivatives.

摘要

针对二乙基亚硝胺诱导的2系豚鼠肝癌的一种致死性、皮内生长的可移植腹水变体(10号线),研发了两种新型免疫治疗方案。在一个明显具有肿瘤特异性的免疫治疗模型中,32只豚鼠在肿瘤攻击后5天或7天,通过向肿瘤区域注射从10号线免疫的2系豚鼠或恒河猴的淋巴组织中获得的同基因或异种RNA提取物而治愈,这是整个治疗方案的一部分,该方案包括在RNA注射之前注射同基因非敏感腹膜渗出细胞,以及在RNA注射之后注射肿瘤特异性抗原。在另一个非肿瘤特异性的免疫治疗模型中,18只2系豚鼠在肿瘤攻击后6天和16天,通过向肿瘤区域注射对纤维蛋白片段E(FFE)特异的抗体而治愈,FFE是纤维蛋白基质形成中的一个重要成分,而纤维蛋白基质被认为在肿瘤发展中起重要作用。当在RNA测试系统中将治疗延迟至12天,或在抗FFE测试系统中将治疗延迟至16天时,肿瘤并未完全消除。50只成功接受治疗的动物的长期存活及其对进一步肿瘤攻击的免疫力表明,这两种免疫治疗程序都具有全身效应。为了进一步验证这一点,在两个部位同时皮内注射10号线细胞,仅对其中一个部位进行治疗。当用抗FFE治疗其中一个肿瘤部位时,观察到治疗的肿瘤完全消退,未治疗的肿瘤生长延迟30%。当用RNA方案治疗该肿瘤部位时,治疗部位和未治疗部位的肿瘤均完全消退。这两种免疫治疗模型及其联合应用的最佳条件尚未确定。尽管如此,这两种免疫治疗方案都比迄今为止报道的针对该肿瘤的任何其他免疫治疗方法更有效,包括使用卡介苗或其衍生物。

相似文献

1
Complete regression of a guinea pig hepatocarcinoma by immunotherapy with "tumor-immune" RNA or antibody to fibrin fragment E.用“肿瘤免疫”RNA或纤维蛋白片段E抗体进行免疫治疗使豚鼠肝癌完全消退。
Isr J Med Sci. 1976 Apr-May;12(4-5):344-59.
2
Complete local tumor regression with antibody to fibrin Fragment E.使用纤维蛋白片段E抗体实现局部肿瘤完全消退。
J Immunol. 1975 Oct;115(4):976-81.
3
Complete and apparently specif local tumor regression using syngeneic or xenogeneic "tumor-immune" RNA extracts.
Cancer Res. 1975 Aug;35(8):1907-14.
4
Tumor regression at an untreated site during immunotherapy of an identical distant tumor.在对远处相同肿瘤进行免疫治疗期间,未治疗部位出现肿瘤消退。
Proc Natl Acad Sci U S A. 1975 Sep;72(9):3680-2. doi: 10.1073/pnas.72.9.3680.
5
A comparison of in vitro cell-mediated reactivity against syngeneic tumor cells by various lymphoid cell populations from Bacillus Calmette-Guérin-tumor-cured, tumor-sensitized, tumor-bearing, and normal inbred guinea pigs.对来自卡介苗-肿瘤治愈、肿瘤致敏、荷瘤和正常近交系豚鼠的各种淋巴细胞群体针对同基因肿瘤细胞的体外细胞介导反应性进行比较。
Cancer Res. 1976 Dec;36(12):4459-66.
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Synergistic effects of active specific immunotherapy and chemotherapy in guinea pigs with disseminated cancer.主动特异性免疫疗法与化疗对荷播散性癌豚鼠的协同作用。
J Immunol. 1983 Jun;130(6):2987-92.
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Isolation and localization of RNA fractions able to transfer tumor-specific delayed hypersensitivity in vitro.能够在体外传递肿瘤特异性迟发型超敏反应的RNA组分的分离与定位。
Cancer Res. 1976 Dec;36(12):4530-6.
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Suppression and immunotherapy of the guinea pig line-10 hepatocarcinoma mediated by nonviable Staphylococcus aureus.非存活金黄色葡萄球菌介导的豚鼠10号线肝癌的抑制与免疫治疗
J Natl Cancer Inst. 1978 Aug;61(2):535-8.
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Inhibition of antibody-complement-mediated killing of tumor cells by hormones.激素对抗体补体介导的肿瘤细胞杀伤作用的抑制
Cancer Res. 1976 Oct;36(10):3672-7.
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Selective localization of tumor-immune spleen cells at the tumor challenge site after adoptive transfer of line 10 tumor immunity in strain 2 guinea pigs.在2系豚鼠中进行10号线肿瘤免疫过继转移后,肿瘤免疫脾细胞在肿瘤攻击部位的选择性定位。
J Immunol. 1985 Mar;134(3):2032-40.

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Some perspectives on the transfer of cell-mediated immunity by immune-RNA.关于免疫核糖核酸介导的细胞免疫转移的一些观点。
Mol Cell Biochem. 1979 May 6;25(1):15-31. doi: 10.1007/BF00211138.