Kaido T J, Maury C, Gresser I
Unite Propre de Recherche, Centre National de la Recerche Scientifique 9045 Institut Federatif de Cancer 1, Villejuif, France.
Cancer Res. 1995 Dec 15;55(24):6133-9.
Effective adoptive immunotherapy of immunocompetent DBA/2 mice challenged i.v. with the highly metastatic ESb T-cell lymphoma required the combined treatment of recipient mice with tumor-sensitized spleen cells and IFN-alpha/beta. In contrast, immune spleen cells and IFN-alpha/beta treatment did not increase the survival time of ESb-injected DBA/2-nu/nu mice, DBA/2-bg/bg mice, or normal DBA/2 mice injected with antibody to CD4. Treatment of immunocompetent DBA/2 mice with antibody to asialo-GM1, silica, dichloromethylene diphosphonate-containing liposomes, or 500 rads whole-body gamma-irradiation did not diminish the antimetastatic action of ESb-immune cells and IFN-alpha/beta. These results indicate that adoptively transferred immune T lymphocytes and IFN-alpha/beta act together with host CD4+ T lymphocytes/factors to inhibit ESb visceral metastases. Combined treatment with ESb-immune cells together with interleukin-1 beta (IL-1 beta), IL-2, tumor necrosis factor-alpha, or granulocyte-macrophage colony-stimulating factor did not increase the survival time of normal DBA/2 mice challenged with ESb cells. In contrast, IL-12, which had only a slight antimetastatic effect when administered alone, did synergize with ESb-immune spleen cells and increased the survival time of ESb-challenged mice to a similar extent as did IFN-alpha/beta and immune spleen cells. Treatment of DBA/2 mice with potent antibody to IFN-alpha/beta did not abrogate the capacity of IL-12 and ESb-immune spleen cells to inhibit ESb metastases. Unlike immunotherapy with ESb-immune cells and IFN-alpha/beta, ESb-immune cells together with IL-12 inhibited ESb metastases in immunodeficient DBA/2-bg/bg mice.
对经静脉注射高转移性ESb T细胞淋巴瘤进行攻击的免疫活性DBA/2小鼠进行有效的过继性免疫治疗，需要用肿瘤致敏脾细胞和IFN-α/β联合治疗受体小鼠。相比之下，免疫脾细胞和IFN-α/β治疗并未延长注射ESb的DBA/2-nu/nu小鼠、DBA/2-bg/bg小鼠或注射抗CD4抗体的正常DBA/2小鼠的存活时间。用抗唾液酸GM1抗体、二氧化硅、含二氯亚甲基二膦酸盐的脂质体或500拉德全身γ射线照射免疫活性DBA/2小鼠，并未削弱ESb免疫细胞和IFN-α/β的抗转移作用。这些结果表明，过继转移的免疫T淋巴细胞和IFN-α/β与宿主CD4+ T淋巴细胞/因子共同作用，以抑制ESb内脏转移。ESb免疫细胞与白细胞介素-1β（IL-1β）、IL-2、肿瘤坏死因子-α或粒细胞-巨噬细胞集落刺激因子联合治疗，并未延长用ESb细胞攻击的正常DBA/2小鼠的存活时间。相比之下，单独给药时仅有轻微抗转移作用的IL-12，确实与ESb免疫脾细胞协同作用，并将受ESb攻击小鼠的存活时间延长至与IFN-α/β和免疫脾细胞相似的程度。用强效抗IFN-α/β抗体治疗DBA/2小鼠，并未消除IL-12和ESb免疫脾细胞抑制ESb转移的能力。与用ESb免疫细胞和IFN-α/β进行免疫治疗不同，ESb免疫细胞与IL-12联合可抑制免疫缺陷的DBA/2-bg/bg小鼠中的ESb转移。
