Bast R C, Zbar B, Mackaness G B, Rapp H J
J Natl Cancer Inst. 1975 Mar;54(3):749-56.
Growth of a murine fibrosarcoma was suppressed when tumor cells were mixed with viable Listeria monocytogenes (LM) before intradermal injection into nonimmune syngeneic recepients. Immunization of recipients, by intravenous injection of LM 11 days before transplantation of LM-tumor cell mixtures, eliminated the mortality associated with large doses of LM but did not alter the antitumor activity of the microorganisms. Simultaneous injection of LM and tumor cells at separate sites failed to affect tumor growth, which suggested that contact between LM and tumor cells was required for tumor suppression. Tumor-specific immunity was not observed; mice surviving injection of LM and tumor cells did not resist a second tumor-cell challenge. At least 100 times more heat-killed LM was required to produce the antitumor effect of viable organisms. The ability of heat-killed LM to suppress tumor growth was abolished by treatment of recipients with rabbit antiserum to mouse thymocytes, which was consistent with a requirement for a host response to the LM. Regression of established fibrosarcoma transplants was produced by the intratumor injection of viable LM 5 days after injection of tumor cells. Intratumor injection of BCG at this interval was not effective. The incidence of tumor regression was not increased by multiple intratumor injections of LM, by intratumor injection of a combination of LM and BCG, or by preimmunization with LM prior to the intratumor injection of the same organism.
当肿瘤细胞与活的单核细胞增生李斯特菌(LM)混合后皮内注射到同基因非免疫受体小鼠体内时,小鼠纤维肉瘤的生长受到抑制。在移植LM-肿瘤细胞混合物前11天通过静脉注射LM对受体进行免疫,消除了与大剂量LM相关的死亡率,但并未改变微生物的抗肿瘤活性。在不同部位同时注射LM和肿瘤细胞未能影响肿瘤生长,这表明肿瘤抑制需要LM与肿瘤细胞之间的接触。未观察到肿瘤特异性免疫;注射LM和肿瘤细胞后存活的小鼠不能抵抗第二次肿瘤细胞攻击。产生抗肿瘤作用所需的热灭活LM至少是活微生物的100倍。用兔抗小鼠胸腺细胞血清处理受体可消除热灭活LM抑制肿瘤生长的能力,这与宿主对LM的反应需求一致。在注射肿瘤细胞5天后通过瘤内注射活的LM可使已建立的纤维肉瘤移植瘤消退。在此间隔时间瘤内注射卡介苗无效。多次瘤内注射LM、瘤内注射LM与卡介苗的组合或在瘤内注射相同微生物之前用LM进行预免疫均未增加肿瘤消退的发生率。