以VEGF及VEGFR2为靶位的抗肿瘤血管生成主动免疫治疗的研究进展

Research Progress of Active Immunotherapies against Tumor Angiogenisis Targeting on VEGF and VEGFR2

肿瘤细胞通过刺激新生血管生成来满足对营养及供氧的不断增长的需求,因此,肿瘤组织生长对于新生血管形成的依赖性使得抗血肿瘤管生成已经成为肿瘤学基础研究与临床治疗领域中最吸引人的策略之一。在众多的促血管生成因子中,血管内皮生长因子(VEGF)及其受体VEGFR2(鼠和人中也分别称为Flk-1和KDR)对于与肿瘤生长、转移及复发相关的血管生成是至关重要的。此外,通过打破肿瘤组织自身介导的免疫耐受与逃避,主动免疫治疗已成为一种崭新的抗肿瘤治疗方法。通过将这两种策略联合应用,抗血管生成主动免疫治疗使得更加有效地抑制肿瘤血管生成成为可能。这种免疫治疗与抗血管生成的联合应用有望成为一种有良好前景的研究方案。本文总结了通过打破VEGF/VEGFR2信号通路实现的抗肿瘤血管生成主动免疫治疗方面最新研究进展。本文讨论了旨在抑制血管生成的三种不同形式的抗肿瘤疫苗--细胞疫苗、蛋白质/多肽疫苗及基因/DNA疫苗,以及这一领域未来的研究方向。

Tumor cells stimulate angiogenesis to meet increasing nutrient and oxygen demands. Therefore, the dependence of growing tumors on new blood vessel formation has made anti-angiogenesis become one of the most appealing strategy in cancer research and therapeutics of clinical oncology. Among all of the factors stimulating angiogenesis, vascular endothelial growth factor （VEGF） and its receptor VEGFR2 （also called fetal liver kinse-1 [Flk-1] in mice, kinase-containing domain receptor [KDR] in humans） are critically important to the angiogenesis associated with tumor growth, metastasis and relapse. In addition, active anti-tumor immunotherapy has provided a novel strategy through interrupting tumor-mediated immune escape and suppression. By combining the two strategies, active anti-angiogenic immunotherapy might offer the possibility to more robustly inhibit tumor angiogenesis. This combination application of immunotherapy and anti-angiogenic treatment might represent a promising avenue for future research. This review summarized latest researches of active immunotherapy targeting tumor angiogenesis through interrupting the signal passway of VEGF/VEGFR2. This paper discussed three different types of vaccines utilized as anti-cancer therapeutics-cell vaccines, protein/peptide vaccines and gene/DNA vaccines-with a specific focus on angiogenesis suppression. And future research directions for this field are also outlined.