Molema G, Meijer D K, de Leij L F
Department of Clinical Immunology, Groningen Utrecht Institute for Drug Exploration, The Netherlands.
Biochem Pharmacol. 1998 Jun 15;55(12):1939-45. doi: 10.1016/s0006-2952(98)00011-2.
Based on their location and central role in solid tumor growth, tumor vascular endothelial cells may present an attractive target for the delivery of therapeutic drugs or cells. The potency of blocking the tumor blood supply in eradicating solid tumors was demonstrated recently in a mouse model of tumor vasculature targeting (Huang et al., Science 275: 547-550, 1997). For clinical application of such strategies, tumor endothelium specific target epitopes need to be identified. Recent studies on angiogenesis have identified angiogenesis-related molecules as potential target epitopes. Among these are vascular endothelial growth factor (VEGF)/VEGF-receptor complex, alpha(v) integrins, and Tie receptor tyrosine kinases. Besides blockade of their signalling cascades leading to inhibition of angiogenesis, these epitopes may also be instrumental in tumor vessel specific delivery of therapeutics. Data on the efficacy of therapeutic modalities aimed at these, mostly heterogeneously distributed tumor endothelial epitopes are scarce, and sophisticated experimentation is required to rationalize the development of new therapeutic strategies. Importantly, only detailed evaluations in cancer patients will provide the blueprint for the development of clinically effective tumor vascular targeted therapies.
基于其在实体瘤生长中的位置和核心作用，肿瘤血管内皮细胞可能是治疗性药物或细胞递送的一个有吸引力的靶点。最近在肿瘤脉管系统靶向的小鼠模型中证实了阻断肿瘤血液供应在根除实体瘤方面的效力（Huang等人，《科学》275: 547 - 550，1997）。对于此类策略的临床应用，需要鉴定肿瘤内皮特异性靶抗原表位。最近关于血管生成的研究已将血管生成相关分子鉴定为潜在的靶抗原表位。其中包括血管内皮生长因子（VEGF）/VEGF受体复合物、α(v)整合素和Tie受体酪氨酸激酶。除了阻断其导致血管生成抑制的信号级联反应外，这些抗原表位在治疗药物的肿瘤血管特异性递送中也可能起作用。针对这些大多异质性分布的肿瘤内皮抗原表位的治疗方式疗效的数据稀缺，需要进行复杂的实验以使新治疗策略的开发合理化。重要的是，只有在癌症患者中进行详细评估才能为开发临床有效的肿瘤血管靶向治疗提供蓝图。
