Ishida H, Kaneda Y, Yamane S, Sawada T, Plautz G E, Matsumura T
Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Anticancer Res. 1999 Nov-Dec;19(6B):5367-73.
In vivo intratumoral gene transfer of allogeneic class I major histocompatibility complex (MHC) genes augments the immune response against weak tumor antigens. In this study, mice inoculated with the allogeneic MHC molecule (H-2Kb), had transduced-murine neuroblastoma C1300S3 cells showed prolonged survival relative to non-transduced or neo transduced tumors (p < 0.005). Interestingly, direct in vivo gene transfer of H-2Kb plasmid DNA complexed with HVJ-liposomes into S3 tumors was highly efficient, resulting in transduction of 8% of the interstitial cells within the tumor but rarely within tumor cells. Regression of established tumors and prolonged survival occurred in 50% of mice injected with H-2Kb, in contrast to no tumor regression in mice receiving control plasmid (p < 0.005). This study concludes that interstitial cells could serve as an important target of intratumoral gene transfer, and further that HVJ-liposome complexes could be a vehicle for in vivo gene transfer.
同种异体I类主要组织相容性复合体(MHC)基因的体内肿瘤内基因转移增强了针对弱肿瘤抗原的免疫反应。在本研究中,接种了同种异体MHC分子(H-2Kb)的小鼠,其转导的鼠神经母细胞瘤C1300S3细胞相对于未转导或新转导的肿瘤显示出更长的生存期(p < 0.005)。有趣的是,将与HVJ-脂质体复合的H-2Kb质粒DNA直接进行体内基因转移到S3肿瘤中效率很高,导致肿瘤内8%的间质细胞被转导,但肿瘤细胞内很少被转导。与接受对照质粒的小鼠无肿瘤消退相比,注射H-2Kb的小鼠中有50%出现了已建立肿瘤的消退和生存期延长(p < 0.005)。本研究得出结论,间质细胞可作为肿瘤内基因转移的重要靶点,进一步表明HVJ-脂质体复合物可作为体内基因转移的载体。