School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, P. R. China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, P. R. China.
Nat Commun. 2024 Jul 23;15(1):6211. doi: 10.1038/s41467-024-50474-y.
The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8 T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.
自然杀伤 (NK) 和 T 细胞在先天和适应性免疫中的功能是互补和交织的。在这里，我们表明，利用能够同时靶向 NK 和 T 细胞的多特异性抗体或纳米抗体可能是癌症免疫治疗的一种有价值的方法。在这里，我们介绍了一种三特异性纳米抗体 (Tri-NAb)，它是通过固定三种类型的单克隆抗体 (mAbs)，使用优化的白蛋白/聚酯复合纳米颗粒与抗 Fc 抗体偶联而产生的。这种三特异性抗体同时靶向 PDL1、4-1BB 和 NKG2A（或 TIGIT），能够有效结合 NK 和 CD8 T 细胞，触发它们的激活和增殖，同时促进它们与肿瘤细胞的相互作用，从而诱导有效的肿瘤杀伤。重要的是，Tri-NAb 的抗肿瘤功效在多个模型中得到了验证，包括患者来源的肿瘤类器官和人源化小鼠，突出了 NK 和 T 细胞共靶向的转化潜力。
