肿瘤细胞治疗研究
英文原题：Anti-HER2 Cancer-Specific mAb, H(2)Mab-250-hG(1), Possesses Higher Complement-Dependent Cytotoxicity than Trastuzumab.
这些结果表明，ADCC和CDC活性对H 2 Mab-250-hG 1和trastuzumab的抗肿瘤效果有不同的贡献，并为H 2 Mab-250-hG 1针对HER2阳性肿瘤的临床开发指明了未来方向。
识别癌症特异性抗原并在体内具有抗肿瘤功效的癌症特异性单克隆抗体（CasMabs）是最大限度减少不良反应的创新治疗策略。我们此前建立了一种癌症特异性抗人表皮生长因子受体2（HER2）单克隆抗体（mAb），H2 Mab-250/H2 CasMab-2。在流式细胞术和免疫组织化学中，H2 Mab-250与HER2阳性乳腺癌细胞反应，但未显示对正常上皮细胞的反应性。相比之下，临床批准的抗HER2 mAb曲妥珠单抗在流式细胞术中强烈识别乳腺癌细胞和正常上皮细胞。H2 Mab-250的人IgG1版本（H2 Mab-250-hG1）对乳腺癌异种移植瘤具有与曲妥珠单抗相当的体内抗肿瘤效果，尽管其体外亲和力和效应激活低于曲妥珠单抗。本研究比较了H2 Mab-250-hG1与曲妥珠单抗的抗体依赖性细胞介导的细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）。在人NK 细胞存在下，H2 Mab-250-hG1和曲妥珠单抗均对HER2过表达的中国仓鼠卵巢-K1和乳腺癌细胞系（BT-474和SK-BR-3）表现出ADCC活性。观察到某种趋势，即曲妥珠单抗相比H2 Mab-250-hG1表现出更显著的ADCC效应。重要的是，与曲妥珠单抗相比，H2 Mab-250-hG1在这些细胞中表现出更优越的CDC活性。在H2 Mab-250和曲妥珠单抗的小鼠IgG2a类型中也获得了类似结果。这些结果表明，ADCC和CDC活性对H 2 Mab-250-hG 1和trastuzumab的抗肿瘤效果有不同的贡献，并为H 2 Mab-250-hG 1针对HER2阳性肿瘤的临床开发指明了未来方向。
Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing adverse effects. We previously established a cancer-specific anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody (mAb), H 2 Mab-250/H 2 CasMab-2. In flow cytometry and immunohistochemistry, H 2 Mab-250 reacted with HER2-positive breast cancer cells but did not show reactivity to normal epithelial cells. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both breast cancer and normal epithelial cells in flow cytometry. The human IgG 1 version of H 2 Mab-250 (H 2 Mab-250-hG 1 ) possesses compatible in vivo antitumor effects against breast cancer xenografts to trastuzumab despite the lower affinity and effector activation than trastuzumab in vitro. This study compared the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDC) between H 2 Mab-250-hG 1 and trastuzumab. Both H 2 Mab-250-hG 1 and trastuzumab showed ADCC activity against HER2-overexpressed Chinese hamster ovary -K1 and breast cancer cell lines (BT-474 and SK-BR-3) in the presence of human natural killer cells. Some tendency was observed where trastuzumab showed a more significant ADCC effect compared to H 2 Mab-250-hG 1 . Importantly, H 2 Mab-250-hG 1 exhibited superior CDC activity in these cells compared to trastuzumab. Similar results were obtained in the mouse IgG 2a types of both H 2 Mab-250 and trastuzumab. These results suggest the different contributions of ADCC and CDC activities to the antitumor effects of H 2 Mab-250-hG 1 and trastuzumab, and indicate a future direction for the clinical development of H 2 Mab-250-hG 1 against HER2-positive tumors.
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