Bright R K, Shearer M H, Pass H I, Kennedy R C
Surgery Department and the Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201-1379, USA.
Dev Biol Stand. 1998;94:341-53.
Various vaccination strategies were compared for their ability to elicit antigen-specific tumour immunity, using the SV40-BALB/c murine tumour system. Specifically, mice were injected with baculovirus-derived recombinant SV40 Tag (rTag), synthetic peptides corresponding to B cell epitopes on SV40 Tag or a plasmid DNA construct encoding the gene for SV40 Tag. In vivo tumour immunity was determined by a lethal tumour challenge with syngeneic SV40-transformed tumour cells. SV40 Tag-specific antibody titres were induced in mice immunized with rTag or Tag synthetic peptides. Partial tumour protection was observed in mice that were immunized with SV40 Tag peptides, where as complete tumour immunity was observed in mice immunized with rTag. Although protective tumour immunity was also observed in mice immunized with DNA, negligible levels of antibodies to SV40 Tag were detected. Examination of the cytotoxic T lymphocyte (CTL) activity in mice injected with the SV40 Tag-DNA construct revealed Tag-specific lysis of syngeneic SV40-transformed tumour cells. Conversely, little to no CTL activity was detected in mice immunized with rTag. However, antigen-specific antibodies from rTag immunized mice were capable of mediating antibody-dependent cell-mediated cytotoxicity against SV40-transformed cells. These data indicate that the immune mechanisms elicited for protection against SV40 induced tumours in mice appeared to be dependent on the vaccination strategy employed and included both humoral and cell-mediated immune responses.
利用SV40-BALB/c小鼠肿瘤系统，比较了各种疫苗接种策略引发抗原特异性肿瘤免疫的能力。具体而言，给小鼠注射杆状病毒衍生的重组SV40 Tag（rTag）、与SV40 Tag上B细胞表位对应的合成肽或编码SV40 Tag基因的质粒DNA构建体。通过用同基因SV40转化的肿瘤细胞进行致死性肿瘤攻击来确定体内肿瘤免疫。在用rTag或Tag合成肽免疫的小鼠中诱导出了SV40 Tag特异性抗体滴度。在用SV40 Tag肽免疫的小鼠中观察到部分肿瘤保护作用，而在用rTag免疫的小鼠中观察到完全肿瘤免疫。尽管在用DNA免疫的小鼠中也观察到了保护性肿瘤免疫，但检测到的针对SV40 Tag的抗体水平可忽略不计。对注射了SV40 Tag-DNA构建体的小鼠的细胞毒性T淋巴细胞（CTL）活性进行检测，结果显示同基因SV40转化的肿瘤细胞出现了Tag特异性裂解。相反，在用rTag免疫的小鼠中几乎未检测到CTL活性。然而，来自rTag免疫小鼠的抗原特异性抗体能够介导针对SV40转化细胞的抗体依赖性细胞介导的细胞毒性作用。这些数据表明，在小鼠中引发的针对SV40诱导肿瘤的免疫机制似乎取决于所采用的疫苗接种策略，并且包括体液免疫和细胞介导的免疫反应。
