Hurpin C, Rotarioa C, Bisceglia H, Chevalier M, Tartaglia J, Erdile L
Pasteur Mérieux Connaught, Marcy L'Etoile, France.
Vaccine. 1998 Jan-Feb;16(2-3):208-15. doi: 10.1016/s0264-410x(97)00190-4.
We have examined the immune response to full-length wild-type human p53 presented by a recombinant canarypox vector (ALVAC) and by plasmid DNA. For the ALVAC recombinant, intravenous, but not subcutaneous, intramuscular or intradermal administration, induced CD8+ CTLs that lysed tumor cells transfected with human mutant p53. Intrasplenic administration also induced CTLs. Biodistribution studies showed that intravenously injected ALVAC localized primarily in the lung, liver and spleen, whereas intramuscularly injected virus remained predominantly at the injection site. Intradermal and intramuscular immunization with naked plasmid DNA encoding human wild-type p53 also induced a specific CTL response. DNA immunization induced complete protection against challenge with a mouse embryo fibroblast transfected with human mutant p53 and partial, but significant, protection against a transfected mastocytoma. The ALVAC recombinant induced partial protection in both models. These results suggest that recombinant ALVAC and DNA might be interesting presentation platforms for p53 to be tested in clinical studies.
我们已经检测了重组金丝雀痘病毒载体（ALVAC）和质粒DNA所呈递的全长野生型人p53的免疫反应。对于ALVAC重组体，静脉内给药（而非皮下、肌肉内或皮内给药）可诱导CD8 + CTL，其能裂解转染了人突变p53的肿瘤细胞。脾内给药也可诱导CTL。生物分布研究表明，静脉注射的ALVAC主要定位于肺、肝和脾，而肌肉注射的病毒主要仍留在注射部位。用编码人野生型p53的裸质粒DNA进行皮内和肌肉内免疫也可诱导特异性CTL反应。DNA免疫可完全保护小鼠免受转染了人突变p53的小鼠胚胎成纤维细胞的攻击，并对转染的肥大细胞瘤提供部分但显著的保护。ALVAC重组体在两种模型中均诱导了部分保护作用。这些结果表明，重组ALVAC和DNA可能是p53在临床研究中值得测试的呈递平台。
