癌胚抗原相关细胞粘附分子1（CEACAM1）是一种广泛研究的细胞表面分子，主要由某些上皮、内皮、淋巴和骨髓细胞表达，是癌症免疫治疗的一个有吸引力的靶点。在此，为了研究CEACAM1抗体的抗肿瘤作用和机制，我们制备了该抗体并探讨了其对非小细胞肺癌（NSCLC）的体外和体内抗肿瘤作用。首先将人CEACAM1重组蛋白抗原免疫BALB/c小鼠，通过杂交瘤技术筛选出高亲和力的鼠抗人单克隆抗体3C11。接下来，采用ELISA检测3C11对CEACAM1-CEACAM1和CEACAM1-CEACAM5的阻断作用。然后，使用细胞测定和ELISA来评估3C11在阻断树突状细胞（DC）与T细胞或自然杀伤细胞（NK）与肿瘤细胞之间的CEACAM1-CEACAM1免疫抑制信号转导中的作用。最后，通过细胞刺激实验和NCI-H358诱导的小鼠肿瘤模型评估了3C11联合抗PD-1抗体的协同抗肿瘤作用。结果显示，3C11 与 NCI-H358 或耗尽的 T 细胞结合的 EC50 分别为 0.04971 μg/mL 和 0.03475 μg/mL。 3C11通过阻断CEACAM1-CEACAM1激活耗尽的T细胞并增强NK的杀伤作用。此外，3C11与抗PD1抗体联合对NSCLC产生协同抗肿瘤作用。其体内抗 PD-1 的肿瘤生长抑制值 (TGI) 从 18% 提高到 85%。这些研究结果表明，3C11 可以被认为是一种有效的 NSCLC 免疫治疗药物。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1), an extensively studied cell surface molecule, mainly expressed by certain epithelial, endothelial, lymphoid and myeloid cells, and is an attractive target for cancer immunotherapy. Here, to investigate the anti-tumor effects and mechanisms of CEACAM1 antibody, we prepared the antibody and explored its anti-tumor effects on Non-small Cell Lung Cancer (NSCLC) in vitro and in vivo. Firstly, antigen of human CEACAM1 recombinant protein was immunized on BALB/c mice and the high-affinity mouse anti-human monoclonal antibody 3C11 was selected by hybridoma technique. Next, ELISA was applied to detect the blocking effects of 3C11 on CEACAM1-CEACAM1 and CEACAM1-CEACAM5. Then, cell assays and ELISA were used to evaluate the role of 3C11 in blocking CEACAM1-CEACAM1 immunosuppressive signal transduction between dendritic cells (DCs) and T cells or natural killer cells (NK) and tumor cells. Finally, the synergistic anti-tumor effect of 3C11 combined with anti-PD-1 antibody was evaluated through cell stimulation assays and NCI-H358-induced tumor models in mice. The results showed the EC50 of 3C11 binding to NCI-H358 or exhausted T cells were 0.04971 μg/mL and 0.03475 μg/mL, respectively. 3C11 activated the exhausted T cells and enhanced the killing effect of NK by blocking CEACAM1-CEACAM1. In addition, the combination of 3C11 and anti-PD1 antibody produced synergistic anti-tumor effect on NSCLC. Its improved tumor growth inhibition value (TGI) of anti-PD-1 from 18 % to 85 % in vivo. These findings suggest that 3C11 can be considered an effective immunotherapy drug for NSCLC.Copyright © 2024 Elsevier B.V. All rights reserved.