Bright R K, Beames B, Shearer M H, Kennedy R C
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228, USA.
Cancer Res. 1996 Mar 1;56(5):1126-30.
Plasmid DNA encoding the large tumor antigen (T- ag) of SV40 was used to actively immunize mice to assess the induction of SV40 T-ag-specific immunity. Mice were injected with the naked DNA i.m., and immune responses were compared to those elicited in mice immunized with the recombinant SV40 T-ag protein. Compared to immunization with the recombinant protein, naked DNA induced weak antibody responses to SV40 T-ag. No increase in natural killer cell activity was observed following either recombinant protein or nucleic acid vaccination. However, the recombinant SV40 T-ag failed to induce SV40 T-ag-specific CTL responses, whereas the plasmid DNA encoding SV40 T-ag elicited CTL activity specific for SV40 T-ag. The SV40 T-ag-specific CTL lysed in vitro only syngeneic target cells (H-2(d)) expressing SV40 T-ag, indicating that the CTL are MHC restricted. Both the recombinant protein and naked DNA preparations induced immune responses that were protective against a lethal challenge with syngeneic SV40-transformed cells. A comparison of recombinant protein versus nucleic acid immunization indicates that both humoral and cell-mediated immune responses may play a role in SV40 T-ag immunity. These data indicate that active immunization with genes encoding tumor-specific antigens may be an efficacious strategy for the induction of tumor immunity.
编码猿猴病毒40（SV40）大肿瘤抗原（T-ag）的质粒DNA被用于主动免疫小鼠，以评估SV40 T-ag特异性免疫的诱导情况。小鼠通过肌内注射裸DNA，其免疫反应与用重组SV40 T-ag蛋白免疫的小鼠所引发的免疫反应进行比较。与用重组蛋白免疫相比，裸DNA诱导的针对SV40 T-ag的抗体反应较弱。重组蛋白或核酸疫苗接种后，自然杀伤细胞活性均未增加。然而，重组SV40 T-ag未能诱导出SV40 T-ag特异性细胞毒性T淋巴细胞（CTL）反应，而编码SV40 T-ag的质粒DNA引发了针对SV40 T-ag的CTL活性。SV40 T-ag特异性CTL仅在体外裂解表达SV40 T-ag的同基因靶细胞（H-2(d)），表明CTL受主要组织相容性复合体（MHC）限制。重组蛋白和裸DNA制剂均诱导了针对同基因SV40转化细胞致死性攻击具有保护作用的免疫反应。重组蛋白与核酸免疫的比较表明，体液免疫和细胞介导的免疫反应可能在SV40 T-ag免疫中均发挥作用。这些数据表明，用编码肿瘤特异性抗原的基因进行主动免疫可能是诱导肿瘤免疫的一种有效策略。
