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部分纯化的肿瘤特异性移植抗原对小鼠3-甲基胆蒽诱导肉瘤肺转移的免疫治疗作用:初步报告

Immunotherapeutic effects of partially purified tumor-specific transplantation antigens on pulmonary metastases of a 3-methylcholanthrene-induced sarcoma in mice: a preliminary report.

作者信息

Tanaka T, Pellis N R, Kahan B D

出版信息

J Natl Cancer Inst. 1982 Nov;69(5):1121-6.

PMID:6957656
Abstract

Tumor-specific transplantation antigens (TSTA), which were partially purified by preparative isoelectric focusing of 3-M KCl extracts of a fibrosarcoma MCA-F induced in inbred female C3H/HeJ mice with 3-methylcholanthrene and previously shown to display immunotherapeutic activity against subcutaneous neoplasms, were effective against pulmonary metastases. Weekly sc injections of 25 micrograms fraction 15 decreased the number of pulmonary colonies after iv injection of tumor cells into syngeneic, virgin C3H/HeJ mice. The effect was immunologically specific; the immunoprotective fraction from the heterotypic, antigenically distinct MCA-D tumor did not affect the number of pulmonary MCA-F tumor colonies. Because fraction 15 treatment did not alter the number of extrapulmonary tumor colonies, the survival rates of hosts challenged iv with MCA-F cells were unaffected. The variant cell line MCA-F-4 was selected to detect prolonged host survival as a result of a therapeutic effect against pulmonary metastases. This line was selected for its proclivity for lung colonization and low propensity for growth in extrapulmonary sites. Cross-immunoprotection tests demonstrated that MCA-F-4 shares a TSTA with the parent tumor. Therapeutic administration of fraction 15 prolonged the survival of hosts in two settings: 1) after artificial iv injection of MCA-F-4 cells and 2) as treatment for hosts resected of 1-cm subcutaneous MCA-F-4 primary tumors and at high risk for spontaneous pulmonary metastases. Therefore, fraction 15 displayed therapeutic effects on both artificially induced and spontaneous pulmonary metastases.

摘要

肿瘤特异性移植抗原(TSTA)是通过对用3-甲基胆蒽在近交系雌性C3H/HeJ小鼠中诱导产生的纤维肉瘤MCA-F的3M KCl提取物进行制备性等电聚焦而部分纯化得到的,先前已证明其对皮下肿瘤具有免疫治疗活性,对肺转移也有效。每周皮下注射25微克的第15组分可减少将肿瘤细胞静脉注射到同基因、未交配的C3H/HeJ小鼠体内后的肺集落数量。该效应具有免疫特异性;来自异型、抗原性不同的MCA-D肿瘤的免疫保护组分不影响肺MCA-F肿瘤集落的数量。由于第15组分处理未改变肺外肿瘤集落的数量,静脉注射MCA-F细胞攻击的宿主的存活率未受影响。选择变异细胞系MCA-F-4来检测由于对肺转移的治疗作用而导致的宿主存活期延长。选择该细胞系是因为其易于在肺部定植且在肺外部位生长倾向低。交叉免疫保护试验表明MCA-F-4与亲本肿瘤共享一种TSTA。第15组分的治疗性给药在两种情况下延长了宿主的存活期:1)在人工静脉注射MCA-F-4细胞后;2)作为对切除1厘米皮下MCA-F-4原发性肿瘤且有自发肺转移高风险的宿主的治疗。因此,第15组分对人工诱导的和自发的肺转移均显示出治疗效果。

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