Effect of the total galactose content on complement-dependent cytotoxicity of the therapeutic anti-CD20 IgG1 antibodies under temperature stress conditions

The degree of monoclonal antibody galactosylation is known to affect complement-dependent cytotoxicity (CDC) activity by affecting C1q binding, suggesting that galactose is associated with CDC bioactivity. However, whether this association also exists under temperature stress conditions is not known. This study highlights the impact of variations in the terminal galactose content of an anti-CD20 monoclonal antibody on CDC bioactivity under high-temperature stress conditions compared with storage conditions at 2–8 °C. Drug product samples with a total galactose content of >38% showed stable CDC bioactivity at higher temperatures (45 °C), while those with 16% galactose content showed reduced CDC activity.

已知单克隆抗体半乳糖基化程度可通过影响补体成分C1q的结合，进而调控补体依赖的细胞毒性（complement-dependent cytotoxicity, CDC）活性，提示半乳糖与CDC生物活性存在关联。然而，该关联在温度应激条件下是否依然成立，目前尚不明确。本研究对比了2~8℃储存条件与高温应激条件下，抗CD20单克隆抗体末端半乳糖含量变化对其CDC生物活性的影响。总半乳糖含量＞38%的药物制剂样品在高温（45℃）下CDC生物活性保持稳定，而半乳糖含量为16%的样品则出现CDC活性下降。