Patel Dipa, Bassi Rajiv, Hooper Andrea T, Sun Haijun, Huber James, Hicklin Daniel J, Kang Xiaoqiang
Department of Experimental Therapeutics and Protein Science, ImClone Systems Incorporated, New York, NY 10014, USA.
Anticancer Res. 2008 Sep-Oct;28(5A):2679-86.
Targeted immunotherapy against tumors or angiogenesis has shown promise as an alternative approach for the treatment of malignant disease. Whether or not combining these two treatment modalities would enhance the antitumor effect was tested in mouse models of malignant melanoma. C57BL/6 mice bearing established subcutaneous B16 tumors were treated with anti-vascular endothelial growth factor receptor (anti-VEGFR) fetal liver kinase-1 (Flk-1) monoclonal antibody (mAb) DC101 and/or anti-TYRP-1/gp75 (tyrosinase-related protein-1) mAb TA99. The growth of subcutaneous B16 tumors was significantly suppressed by the mAb DC101 (63%, p<0.001) and by mAb TA99 (75%, p<0.001) treatment alone. The combined antibody (TA99+DC101) treatment resulted in a significant enhancement (93%, p<0.001) of tumor growth suppression. In a B16 pulmonary metastasis model, combined therapy with mAb DC101 and mAb TA99 resulted in a significant reduction of lung metastases compared to the control (p<0.001) and the single agent treatment groups (p<0.05). A combined modality approach that provides passive immunity to melanoma differentiation antigens as well as inhibiting tumor neovascularization may be valuable for the treatment of malignant melanoma.
针对肿瘤或血管生成的靶向免疫疗法已显示出有望成为治疗恶性疾病的替代方法。在恶性黑色素瘤小鼠模型中测试了联合使用这两种治疗方式是否会增强抗肿瘤效果。用抗血管内皮生长因子受体（抗VEGFR）胎儿肝激酶-1（Flk-1）单克隆抗体（mAb）DC101和/或抗TYRP-1/gp75（酪氨酸酶相关蛋白-1）mAb TA99治疗已建立皮下B16肿瘤的C57BL/6小鼠。单独使用mAb DC101（63%，p<0.001）和mAb TA99（75%，p<0.001）治疗可显著抑制皮下B16肿瘤的生长。联合抗体（TA99+DC101）治疗导致肿瘤生长抑制显著增强（93%，p<0.001）。在B16肺转移模型中，与对照组（p<0.001）和单药治疗组（p<0.05）相比，mAb DC101和mAb TA99联合治疗导致肺转移显著减少。一种既能提供针对黑色素瘤分化抗原的被动免疫又能抑制肿瘤新生血管形成的联合治疗方法可能对恶性黑色素瘤的治疗有价值。
