Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan.
Int J Cancer. 2013 Feb 1;132(3):717-25. doi: 10.1002/ijc.27700. Epub 2012 Jul 14.
The use of Salmonella as a potential antitumor agent has been investigated, but innate immunity against this bacterium reduces the efficacy of its tumor-targeting and antitumor activities. The purpose of this study was to investigate the modulation of the tumor-targeting efficiency of Salmonella enterica serovar choleraesuis by modifying the immune response to these bacteria by coating them with poly(allylamine hydrochloride) (PAH), designated PAH-S.C. To evaluate this modulation, we used naïve mice and mice immunized with Salmonella to study the role of the preexisting immune response to the antitumor activity of PAH-S.C. When anti-Salmonella antibodies were present, the invasion activity, cytotoxicity, and gene transfer of Salmonella was significantly decreased, both in vitro and in vivo. Treatment with PAH-S.C. resulted in delayed tumor growth and enhanced survival in immunized mice. Furthermore, immunohistochemical studies of the tumors revealed the infiltration of neutrophils and macrophages in immunized mice treated with PAH-S.C. These results indicate that Salmonella encapsulation effectively circumvented the Salmonella-specific immune response.
已研究将沙门氏菌用作潜在的抗肿瘤剂，但机体对这种细菌的固有免疫会降低其肿瘤靶向和抗肿瘤活性。本研究旨在通过用聚（盐酸烯丙胺）（PAH）对沙门氏菌肠亚种（S. choleraesuis）进行包被，修饰针对这些细菌的免疫反应，从而提高沙门氏菌的肿瘤靶向效率。为了评估这种调节作用，我们使用了未免疫的小鼠和经沙门氏菌免疫的小鼠，研究了针对 PAH-S.C. 的抗肿瘤活性的预先存在的免疫反应的作用。当存在抗沙门氏菌抗体时，沙门氏菌的侵袭活性、细胞毒性和基因转移在体外和体内均显著降低。用 PAH-S.C. 处理可导致免疫小鼠的肿瘤生长延迟和存活率提高。此外，对用 PAH-S.C. 处理的免疫小鼠的肿瘤进行免疫组织化学研究显示，中性粒细胞和巨噬细胞浸润。这些结果表明，沙门氏菌包被可有效规避针对沙门氏菌的免疫反应。
