抗体药物偶联物 (ADC) 提供了一种有前景的方法，将单克隆抗体与化疗药物相结合，有效靶向癌细胞，同时最大限度地降低毒性。本研究探讨了双特异性 ADC (BsADC) 在喉鳞状细胞癌中的治疗效果和潜在机制。该 BsADC 选择性地靶向免疫检查点程序性细胞死亡配体-1 (PD-L1) 和 B7-H3，并精确递送小分子毒素单甲基 auristatin E。我们的研究结果表明，BsADC 的性能优于其双特异性抗体和 PD- L1 或 B7-H3 ADC 对应物，特别是在体外/体内肿瘤细胞毒性方面，表现出显着的免疫细胞毒性。此外，我们观察到肿瘤特异性免疫的有效激活以及免疫原性细胞死亡（ICD）标记物和潜在内质网应激的显着诱导。总之，这种新型 BsADC 通过免疫检查点抑制和 ICD 促进，放大了持久的肿瘤免疫细胞毒性，为未来的癌症治疗和克服耐药性提供新颖的见解和潜在途径。© 作者（或其雇主）2024。根据 CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity.This study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl auristatin E.Our findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress.In conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.