Siesjö P, Visse E, Sjögren H O
Department of Tumor Immunology, University Hospital, Lund, Sweden.
J Immunother Emphasis Tumor Immunol. 1996 Sep;19(5):334-45.
We have previously reported that immunizations with mutagen-induced immunogenic variants of a weakly immunogenic rat glioma could protect against isografts of the original tumor cells. In this study we show that prolonged survival and cures of rats with established gliomas in their brains can be achieved by therapeutic immunizations with tumor cell mutants, combined with in vitro and in vivo interferon (IFN)-gamma (adjuvant) treatment, or tumor cells admixed with semipurified syngeneic dendritic cells. Cure of rats with established intracerebral gliomas was possible when immunizations were initiated up to 5 days after intracerebral isografting of original tumor cells. Unexpectedly, immunizations combined with in vitro and in vivo IFN-gamma treatment or with admixed semipurified dendritic cells equalized the immunogenic potential of the original tumor cells and that of mutagen-induced immunogenic cell variants (tum-). This demonstrates that effective immunizations against a weakly immunogenic brain tumor can be achieved by different adjuvant concepts. The therapeutic effect of immunizations with tumor cells admixed with semipurified dendritic cells was highly significant in female rats, whereas only occasional cures and prolonged survival were recorded in male rats. The overall results show that therapeutic immunizations can indeed be effective against an established and growing intracerebral tumor.
我们之前报道过，用弱免疫原性大鼠胶质瘤的诱变诱导免疫原性变体进行免疫接种，可以预防原始肿瘤细胞的同基因移植。在本研究中，我们表明，通过用肿瘤细胞突变体进行治疗性免疫接种，结合体外和体内干扰素（IFN）-γ（佐剂）治疗，或与半纯化同基因树突状细胞混合的肿瘤细胞，可以使患有脑部已形成胶质瘤的大鼠延长生存期并治愈。当在原始肿瘤细胞脑内同基因移植后5天内开始免疫接种时，患有脑内胶质瘤的大鼠有可能被治愈。出乎意料的是，免疫接种与体外和体内IFN-γ治疗或与混合的半纯化树突状细胞相结合，使原始肿瘤细胞和诱变诱导的免疫原性细胞变体（tum-）的免疫原性潜力相等。这表明，通过不同的佐剂概念可以实现针对弱免疫原性脑肿瘤的有效免疫接种。用与半纯化树突状细胞混合的肿瘤细胞进行免疫接种的治疗效果在雌性大鼠中非常显著，而在雄性大鼠中仅偶尔有治愈和生存期延长的记录。总体结果表明，治疗性免疫接种确实可以有效对抗已形成并生长的脑内肿瘤。
