Toes R E, Offringa R, Blom R J, Melief C J, Kast W M
Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands.
Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7855-60. doi: 10.1073/pnas.93.15.7855.
Vaccination with synthetic peptides representing cytotoxic T lymphocyte (CTL) epitopes can lead to a protective CTL-mediated immunity against tumors or viruses. We now report that vaccination with a CTL epitope derived from the human adenovirus type 5 E1A-region (Ad5E1A234-243), which can serve as a target for tumor-eradicating CTL, enhances rather than inhibits the growth of Ad5E1A-expressing tumors. This adverse effect of peptide vaccination was rapidly evoked, required low doses of peptide (10 micrograms), and was achieved by a mode of peptide delivery that induces protective T-cell-mediated immunity in other models. Ad5E1A-specific CTL activity could no longer be isolated from mice after injection of Ad5E1A-peptide, indicating that tolerization of Ad5E1A-specific CTL activity causes the enhanced tumor outgrowth. In contrast to peptide vaccination, immunization with adenovirus, expressing Ad5E1A, induced Ad5E1A-specific immunity and prevented the outgrowth of Ad5E1A-expressing tumors. These results show that immunization with synthetic peptides can lead to the elimination of anti-tumor CTL responses. These findings are important for the design of safe peptide-based vaccines against tumors, allogeneic organ transplants, and T-cell-mediated autoimmune diseases.
用代表细胞毒性T淋巴细胞（CTL）表位的合成肽进行疫苗接种可引发针对肿瘤或病毒的由CTL介导的保护性免疫。我们现在报告，用源自人5型腺病毒E1A区域（Ad5E1A234 - 243）的CTL表位进行疫苗接种，该表位可作为根除肿瘤的CTL的靶标，却增强而非抑制表达Ad5E1A的肿瘤的生长。肽疫苗接种的这种不良效应迅速出现，所需肽剂量低（10微克），并且是通过在其他模型中诱导保护性T细胞介导免疫的肽递送方式实现的。注射Ad5E1A肽后，无法再从小鼠中分离出Ad5E1A特异性CTL活性，这表明Ad5E1A特异性CTL活性的耐受导致肿瘤生长增强。与肽疫苗接种相反，用表达Ad5E1A的腺病毒免疫诱导了Ad5E1A特异性免疫，并阻止了表达Ad5E1A的肿瘤的生长。这些结果表明，用合成肽免疫可导致抗肿瘤CTL反应的消除。这些发现对于设计针对肿瘤、同种异体器官移植和T细胞介导的自身免疫性疾病的安全的基于肽的疫苗具有重要意义。
