PHASE I CH14.18 AND R24 MOAB AND IL-2 FOR PATIENTS WITH GD2+/GD3+

我们的实验室已经证明了ch14.18的能力 单克隆抗体（MoAb）介导抗体依赖性细胞 如果测试的效应细胞首先具有细胞毒性（ADCC）， 用白细胞介素-2（IL-2）激活。 同样，细胞毒性 体内激活的淋巴因子激活的杀伤（LAK）细胞可以 在体外通过R24抗体增强。 我们还证明， 在体外，更多的小细胞癌细胞、神经母细胞瘤细胞和 黑色素瘤细胞在暴露于ch14.18 抗体和R24单抗比当暴露于单独的单抗。 因此，基于这些临床前数据，我们的目标是确定 ch14.18、R24和 转移性黑色素瘤、软组织肉瘤或 广泛期肺小细胞癌，或 肿瘤结合ch14.18或R24单克隆抗体， 免疫组织化学染色。

Our laboratory has demonstrated that the ability of the ch14.18 monoclonal antibody (MoAb) to mediate antibody-dependent cellular cytotoxicity (ADCC) is enhanced if the effector cells tested have first been activated with interleukin-2 (IL-2). Similarly, the cytotoxicity of in vivo activated lymphokine activated killer (LAK) cells can be augmented in vitro by the R24 antibody. We have also demonstrated that in vitro, more small cell carcinoma cells, neuroblastoma cells and melanoma cells bind MoAb when exposed to a combination of the ch14.18 antibody and R24 MoAb than when exposed to either MoAb alone. Therefore, based upon this preclinical data, our goals are to determine the tolerability and toxicity of a combination of ch14.18, R24, and IL-2 in patients with metastatic melanoma, soft tissue sarcomas, or extensive stage small cell carcinoma of the lung, or in patients whose tumor binds either the ch14.18 or R24 MoAb as demonstrated by immunohistochemical staining.