Blood Cancer J. 2012 Apr;2(4):e67. doi: 10.1038/bcj.2012.12. Epub 2012 Apr 20.
We established a mouse model of microenvironment-dependent human lymphoma, and assessed the therapeutic potential of bevacizumab, an antitumor agent acting on the microenvironment. NOD/Shi-scid, IL-2Rγ(null) (NOG) mice were used as recipients of primary tumor cells from a patient with diffuse large B-cell lymphoma (DLBCL), which engraft and proliferate in a microenvironment-dependent manner. The lymphoma cells could be serially transplanted in NOG mice, but could not be maintained in in vitro cultures. Injection of bevacizumab together with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) significantly increased necrosis and decreased vascularization in the tumor, compared with CHOP alone. Levels of human soluble interleukin-2 receptor (sIL2R) in the serum of bevacizumab+CHOP-treated mice (reflecting the DLBCL tumor burden) were significantly lower than in CHOP recipients. Mice receiving bevacizumab monotherapy also showed significant benefit in terms of tumor necrosis and vascularization, as well as decreased serum sIL2R concentrations. The present DLBCL model reflects the human DLBCL in vivo environment more appropriately than current mouse models using established tumor cell lines. This is the first report to evaluate the efficacy of bevacizumab in such a tumor microenvironment-dependent model. Bevacizumab may be a potential treatment strategy for DLBCL patients.
我们建立了一个依赖微环境的人淋巴瘤小鼠模型，并评估了贝伐单抗（一种作用于微环境的抗肿瘤药物）的治疗潜力。我们使用 NOD/Shi-scid，IL-2Rγ（null）（NOG）小鼠作为弥漫性大 B 细胞淋巴瘤（DLBCL）患者原代肿瘤细胞的受体，这些细胞以依赖微环境的方式植入和增殖。淋巴瘤细胞可以在 NOG 小鼠中连续移植，但不能在体外培养中维持。与单独使用 CHOP（环磷酰胺、多柔比星、长春新碱、泼尼松龙）相比，贝伐单抗联合 CHOP 注射显著增加了肿瘤的坏死并减少了血管生成。贝伐单抗+CHOP 治疗组小鼠血清中人可溶性白细胞介素 2 受体（sIL2R）水平（反映 DLBCL 肿瘤负担）明显低于 CHOP 组。接受贝伐单抗单药治疗的小鼠在肿瘤坏死和血管生成以及血清 sIL2R 浓度降低方面也表现出显著获益。与使用已建立的肿瘤细胞系的当前小鼠模型相比，该 DLBCL 模型更能反映体内的人类 DLBCL 环境。这是首次在这种肿瘤微环境依赖模型中评估贝伐单抗疗效的报告。贝伐单抗可能是 DLBCL 患者的一种潜在治疗策略。
