Ichinose Y, Okino T, Yamasaki S, Moriguchi Y, Sugie T, Li L, Kanaoka S, Kan N, Watanabe Y, Imamura M
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Japan.
Surg Today. 1999;29(4):338-43. doi: 10.1007/BF02483058.
To evaluate the effect of interferon-gamma-gene-transduced cells, DS mice were inoculated into their footpads with syngeneic mammary adenocarcinoma SC42 admixed with interferon-gamma producing mammary adenocarcinoma SC115Kgamma, which had been established by an interferon-gamma-gene transduction in another syngeneic mammary adenocarcinoma SC115 using retroviral vectors. These mice rejected both tumor cells and developed resistance to subsequent challenges with either SC115 or SC42 cells inoculated into their opposite posterior footpads. These results thus indicate that systemic immunological memory to each of the independent tumor cell lines developed in these mice. Although the SC42 cells admixed with irradiated SC115Kgamma cells were rejected by these mice, the SC42 cells admixed with irradiated SC115neoR, in which the neo-gene had been transduced, were observed to proliferate. Tumor rejection was reversed by an in vivo administration of anti-interferon-gamma antibody, thus suggesting that locally produced interferon-gamma plays an important role in tumor elimination and immunological memory induction. In conclusion, interferon-gamma-gene-transduced tumor cells are therefore considered to have a therapeutic potential for other types of malignant tumor cell lines.
为了评估干扰素-γ基因转导细胞的效果，将同基因乳腺腺癌SC42与产生干扰素-γ的乳腺腺癌SC115Kγ混合后接种到DS小鼠的足垫中，SC115Kγ是通过逆转录病毒载体将干扰素-γ基因转导至另一种同基因乳腺腺癌SC115中建立的。这些小鼠排斥了两种肿瘤细胞，并对随后接种到其对侧后足垫的SC115或SC42细胞的攻击产生了抗性。因此，这些结果表明这些小鼠对每种独立的肿瘤细胞系都产生了全身性免疫记忆。尽管与经辐照的SC115Kγ细胞混合的SC42细胞被这些小鼠排斥，但观察到与经辐照的转导了新霉素基因的SC115neoR混合的SC42细胞发生了增殖。体内给予抗干扰素-γ抗体可逆转肿瘤排斥反应，这表明局部产生的干扰素-γ在肿瘤消除和免疫记忆诱导中起重要作用。总之，因此认为干扰素-γ基因转导的肿瘤细胞对其他类型的恶性肿瘤细胞系具有治疗潜力。
