The disialoganglioside, GD2, is a promising therapeutic target due to its overexpression in certain tumors, particularly neuroblastoma (NB), with limited expression in normal tissues. Despite progress, the intricate mechanisms of action and the full spectrum of the direct cellular responses to anti-GD2 antibodies remain incompletely understood. In this study, we examined the direct cytotoxic effects of the humanized anti-GD2 antibody hu14.18K322A (hu14) on NB cell lines, by exploring the associated cell-death pathways. Additionally, we assessed the synergy between hu14 and conventional induction chemotherapy drugs. Our results revealed that hu14 treatment induced direct cytotoxic effects in CHLA15 and SK-N-BE1 cell lines, with a pronounced impact on proliferation and colony formation. Apoptosis emerged as the predominant cell-death pathway triggered by hu14. Furthermore, we saw a reduction in GD2 surface expression in response to hu14 treatment. Hu14 demonstrated synergy with induction chemotherapy drugs with alterations in GD2 expression. Our comprehensive investigation provides valuable insights into the multifaceted effects of hu14 on NB cells, shedding light on its direct cytotoxicity, cell-death pathways, and interactions with induction chemotherapy drugs. This study contributes to the evolving understanding of anti-GD2 antibody therapy and its potential synergies with conventional treatments in the context of NB.
双唾液酸神经节苷脂GD2因其在特定肿瘤（尤其是神经母细胞瘤）中过度表达而在正常组织中表达有限，成为一个有前景的治疗靶点。尽管已有进展，但抗GD2抗体的复杂作用机制及其引发的直接细胞反应谱仍未完全阐明。本研究通过探究相关细胞死亡通路，考察了人源化抗GD2抗体hu14.18K322A（hu14）对神经母细胞瘤细胞系的直接细胞毒性作用。同时，我们评估了hu14与常规诱导化疗药物之间的协同效应。结果显示，hu14处理能诱导CHLA15和SK-N-BE1细胞系产生直接细胞毒性作用，显著抑制细胞增殖和集落形成。细胞凋亡是hu14引发的主要细胞死亡途径。此外，hu14处理可降低GD2的表面表达。当GD2表达发生改变时，hu14与诱导化疗药物表现出协同作用。我们的综合研究为hu14对神经母细胞瘤细胞的多方面影响提供了重要见解，揭示了其直接细胞毒性、细胞死亡通路以及与诱导化疗药物的相互作用。这项研究有助于深化对抗GD2抗体疗法及其与常规治疗在神经母细胞瘤中潜在协同作用的理解。
肿瘤(癌症)患者之家