免疫检查点抑制剂（ICI）的抗药性需要获取新的策略，以扩大对晚期癌症的治疗手段。双特异性抗体可以作为一种新兴的治疗范式和癌症免疫治疗的一个进一步步骤。同时抑制程序性死亡受体1（PD-1）、程序性死亡配体1（PD-L1）或细胞毒性T淋巴细胞相关抗原4（CTLA-4），或与其他药物联用，可以通过紧密维持肿瘤免疫微环境（TIME）中的细胞-细胞桥（称为免疫突触）来扩大抗体的选择性和提高治疗窗口。事实上，与单一药物的组合单克隆抗体治疗相比，这种共同靶向方法在刺激抗肿瘤免疫反应、减缓肿瘤生长和改善患者生存方面具有更高的效力。事实上，这种双特异性抗体与TIME细胞的相互作用形成的免疫突触直接介导了对肿瘤细胞的细胞毒性，并且在应用这种双特异性抗体后可以预测到持久的抗肿瘤免疫反应。此外，与单独使用检查点抑制剂相比，双特异性抗体的不良事件更少。所有这些都表明，利用新的双特异性方法作为传统组合检查点抑制剂治疗的替代方案特别适用于免疫抑制或免疫冷漠性肿瘤的重要性。在这个领域的研究仍在继续，未来会更多地了解这种双特异性方法在癌症免疫治疗中的重要性。版权所有©2023年作者。由爱思唯尔大专出版社发表。保留所有权利。

Immune checkpoint inhibitor (ICI) resistance demands for acquisition of novel strategies in order to broaden the therapeutic repertoire of advanced cancers. Bispecific antibodies can be utilized as an emerging therapeutic paradigm and a step forward in cancer immunotherapy. Synchronous inhibition of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1) or cytotoxic T lymphocyte associated antigen-4 (CTLA-4), or with other agents can expand antibody selectivity and improve therapeutic window through tightening cell-to-cell bridge (a process called immunological synapse) within tumor immune microenvironment (TIME). There is evidence of higher potency of this co-targeting approach over combined single-agent monoclonal antibodies in reinvigorating anti-tumor immune responses, retarding tumor growth, and improving patient survival. In fact, immunological synapses formed by interactions of such bispecific agents with TIME cells directly mediate cytotoxicity against tumor cells, and durable anti-tumor immune responses are predictable after application of such agents. Besides, lower adverse events are reported for bispecific antibodies compared with individual checkpoint inhibitors. These are all indicative of the importance of exploiting novel bispecific approach as a replacement for conventional combo checkpoint inhibitor therapy particularly for tumors with immunosuppressive or cold immunity. Study in this area is still continued, and in the future more will be known about the importance of this bispecific approach in cancer immunotherapy.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.