Bensussan Armand, Bizzini Bernard, Pouletty Philippe, Gallo Robert C, Zagury Daniel
Institut National de la Santé et de la Recherche Médicale, Inserm U841, Créteil, France.
Med Sci (Paris). 2008 Mar;24(3):306-13. doi: 10.1051/medsci/2008243306.
The abnormal cytokine release in the stromal microenvironment of pathologic tissues, contributes to the pathogenesis of viral infections such as AIDS, cancer and auto-immune diseases. Neovacs developed therapeutic vaccines, named Kinoids, which induce anti-cytokine Antibodies. Kinoids are non toxic but immunogenic cytokine derivatives. Kinoid immunizations induce high titre of neutralizing Abs to the corresponding cytokine, is well tolerated and experimentally effective. In transgenic mice expressing huTNFalpha, the TNFalpha kinoid decreases clinical signs of Rheumatoid Arthritis and in mice challenged with syngenic CT26 tumor cell line huVEGF kinoid inhibits lung metastases. After validation by clinical trials, kinoid vaccines could represent a second generation of specific immune therapy to be used to combat ectopic cytokines.
病理组织基质微环境中细胞因子的异常释放,促成了诸如艾滋病、癌症和自身免疫性疾病等病毒感染的发病机制。Neovacs研发了名为Kinoids的治疗性疫苗,可诱导产生抗细胞因子抗体。Kinoids是无毒但具有免疫原性的细胞因子衍生物。Kinoid免疫接种可诱导产生针对相应细胞因子的高滴度中和抗体,耐受性良好且在实验中有效。在表达人肿瘤坏死因子α(huTNFalpha)的转基因小鼠中,TNFalpha Kinoid可减轻类风湿性关节炎的临床症状,在用同基因CT26肿瘤细胞系攻击的小鼠中,huVEGF Kinoid可抑制肺转移。经临床试验验证后,Kinoid疫苗可能代表用于对抗异位细胞因子的第二代特异性免疫疗法。