摘要
目的 :探索点突变 p5 3抗原肽重组痘苗病毒诱导的抗瘤免疫效应 ,以及B7对之的加强作用 ,为重组抗原肽疫苗用于肿瘤免疫治疗提供实验依据。方法 :选择人 135位Cys→Tyr点突变p5 3为肿瘤相关抗原模型 ,观察包含该点突变p5 3抗原肽p5 312 5~ 14 5的重组痘苗病毒rVV p5 3M 单独和联合应用表达B7的重组痘苗病毒rVV B7诱导的CTL及对荷瘤小鼠的免疫保护和治疗效应。结果 :以rVV p5 3M 经静脉免疫BALB/c小鼠能够诱导以CD8+ T细胞为主的特异性CTL。rVV p5 3M 能够保护部分小鼠免遭致死剂量的肿瘤细胞攻击。以rVV p5 3M 治疗荷瘤小鼠 ,可显著延长小鼠平均存活时间。rVV B7与rVV p5 3M 以 1∶1的比例混合接种可加强rVV p5 3M诱导的抗瘤免疫反应。结论 :以痘苗病毒为载体的p5 3抗原肽疫苗可代替人工合成抗原肽 ,有潜在的临床应用价值 ,共刺激分子B7与肿瘤抗原相结合是一种有效的免疫治疗策略。
Objective: To explore antitumor responses induced by recombinant vaccinia viruses expressing a p53 antigenic peptide (rVV p53 M) and enhanced effect of recombinant vaccinia viruses expressing costimulatory molecule B7 (rVV B7). Methods: A 135 Cys to Tyr point mutation p53 transduced P815 mastocytoma (P815 mp53) was used as an experimental tumor and the p53 protein as the model of tumor associated antigen. rVV p53 M and rVV B7 were used as vaccine to test their induction of CTL and antitumor immunity. Results: Immunization of BABL/c mice with rVV p53 M could elicit specific CTLs, which could specifically lyse P815 mp53 cells. Immunization of mice with rVV p53 M could survive a part of mice challenged with 1×10 6 P815 mp53. Treatment with rVV p53 M could significantly prolong the survival of tumor bearing mice. Admixture at 1∶1 ratio of rVV p53 M and rVV B7 could enhance antitumor responses induced by rVV p53 M. Conclusion: Immunization with recombinant vaccinia virus expressing antigenic peptide is a useful alternative to peptide based vaccine. Costimulatory molecule B7 can enhance antigenic peptide to induce antitumor responses.
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
2000年第4期261-264,共4页
Chinese Journal of Cancer Biotherapy