A pilot trial of vitaxin, a humanized anti-vitronectin receptor (anti αvβ3) antibody in patients with metastatic cancer
A pilot trial of vitaxin, a humanized anti-vitronectin receptor (anti αvβ3) antibody in patients with metastatic cancer
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DOI：
10.1089/108497801300189218
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发表时间：
2001-04-01
影响因子：
3.4
通讯作者：
LoBuglio, AF
中科院分区：
文献类型：
--
作者：
Posey, JA;Khazaeli, MB;LoBuglio, AF
进展性恶性肿瘤的血管生成反应的特征是刺激因子？平衡的变化：和血管生成抑制因子。识别肿瘤血管生成的调控步骤为开发抗肿瘤治疗提供了独特的靶点。Vitaxin是一种人源化单克隆抗体，对整合素α v β 3（玻连蛋白受体）具有特异性。这种抗体可以在体外损害血管内皮细胞生长因子的反应，并抑制肿瘤细胞介导的血管生成在临床前动物模型中，标准治疗失败的转移性癌症患者在三名患者的队列中接受10，50或200毫克的静脉内剂量。在治疗周期的第0天和第21天输注未标示剂量的Vitaxin。所有患者均接受治疗前成像剂量为1 mg的Tc-99 m Vitaxin，并进行伽马相机成像研究。在这三个剂量水平中未观察到显著毒性。无客观抗肿瘤缓解。3名患者接受了2个周期的治疗，在第85天停止研究时病情稳定，尽管1名α（v）β（3）阳性黑色素瘤患者进行了肿瘤部位的成像，但肿瘤血管的放射成像不成功。所有患者均未出现对Vitaxin的免疫应答。接受10 mg剂量Vitaxin的患者具有注射剂量的不良血浆恢复和血浆中的短暂循环。50和200 mg剂量的血浆回收率更接近约7天的血浆和循环半衰期中的预测水平。这些数据表明，每三周一次的Vitaxin剂量为200 mg（2.5 - 3.5 mg/kg）的时间表可以维持？抗体循环水平，毒性很小或没有毒性。未来的研究将挑战定义恶性肿瘤中的抗肿瘤活性或抗肿瘤作用的适当替代物，并探索递增剂量和替代给药方案。
The angiogenic response of a progressing malignancy is characterized by a shift in the balance of stimulator?: and inhibiting factors of angiogenesis. Recognition of the regulated steps in tumor angiogenesis provides unique targets for developing anti-tumor therapy. Vitaxin is a humanized monoclonal antibody, which has specificity for the integrin alpha v beta 3 (vitronectin receptor). This antibody can impair the vascular response of ei endothelial cell growth factors in vitro and inhibit rumor cell mediated angiogenesis in pre-clinical animal models.Patients with metastatic cancer who failed standard therapy received intravenous doses of 10, 50 or 200 mg in cohorts of three patients. The unlabeled dose of Vitaxin was infused on days 0 and 21 of a treatment cycle. All patients received a pre-therapy imaging dose of 1 mg of Tc-99m Vitaxin with gamma camera imaging studies. There was no significant toxicity noted in these three dose levels. There were no objective anti-tumor responses. Three patients received two cycles of therapy and had stable disease at day 85 when taken off study.Radioimaging of tumor vasculature was unsuccessful although one patient with alpha (v)beta (3) positive melanoma had imaging of tumor sites. There was no immune response to Vitaxin in any patient. Patients receiving 10 mg doses of Vitaxin had poor plasma recovery of injected doses and brief circulation in plasma. Doses of 50 and 200 mg had plasma recovery that better approximated the predicted levels in plasma and circulation half-lilies of approximately 7 days. This data suggests that an every three-week schedule of Vitaxin at doses of 200 mg (2.5 - 3.5 mg/kg) can maintain? circulating levels of antibody with little or no toxicity. Future studies will be challenged to define anti-tumor activity in malignancy or appropriate surrogates of anti-tumor effect and explore escalating doses and alternate schedules of administration.