Recombinant Antibodies Laboratory, Dept. of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Cubanacán, Playa Havana 10600, Cuba.
Vaccine. 2010 Apr 26;28(19):3453-61. doi: 10.1016/j.vaccine.2010.02.069. Epub 2010 Mar 1.
We have developed a cancer vaccine candidate (hereafter denominated CIGB-247), based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, and the adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). In mice, previous work of our group had shown that vaccination with CIGB-247 extended tumor-take time, slowed tumor growth, and increased animal survival. Immunization elicited anti-human and murine VEGF-neutralizing antibodies, and spleen cells of vaccinated mice are cytotoxic in vitro to tumor cells that produce VEGF. We have now tested the immunogenicity of CIGB-247 in Wistar rats, New Zealand White rabbits and the non-human primate Chlorocebus aethiops sabaeus. Using weekly, biweekly and biweekly plus montanide immunization schemes, all three species develop antigen-specific IgG antibodies that can block the interaction of VEGF and VEGF receptor 2 in an ELISA assay. Antibody titers decline after vaccination stops, but can be boosted with new immunizations. In monkeys, DTH and direct cell cytotoxicity experiments suggest that specific T-cell responses are elicited by vaccination. Immunization with CIGB-247 had no effect on normal behavior, hematology, blood biochemistry and histology of critical organs, in the tested animals. Skin deep wound healing was not affected in vaccinated rats and monkeys.
我们已经开发出一种癌症疫苗候选物（以下简称 CIGB-247），它基于重组修饰的人血管内皮生长因子（VEGF）作为抗原，以及佐剂 VSSP（脑膜炎奈瑟菌外膜的非常小尺寸蛋白脂质体）。在小鼠中，我们小组之前的工作表明，用 CIGB-247 进行疫苗接种可以延长肿瘤潜伏期、减缓肿瘤生长并提高动物存活率。免疫接种可引发抗人及鼠 VEGF 的中和抗体，且接种小鼠的脾细胞在体外对产生 VEGF 的肿瘤细胞具有细胞毒性。我们现在已经在 Wistar 大鼠、新西兰白兔和非人类灵长类动物 Chlorocebus aethiops sabaeus 中测试了 CIGB-247 的免疫原性。使用每周、每两周和每两周加 montanide 免疫方案，这三种物种均产生可在 ELISA 测定中阻断 VEGF 与 VEGF 受体 2 相互作用的抗原特异性 IgG 抗体。疫苗接种停止后抗体滴度下降，但可通过新的免疫接种增强。在猴子中，DTH 和直接细胞细胞毒性实验表明，疫苗接种可引发特异性 T 细胞反应。在受测试的动物中，用 CIGB-247 进行免疫接种对正常行为、血液学、血液生化学和关键器官的组织学没有影响。接种大鼠和猴子的皮肤深部伤口愈合不受影响。
