A CD276-Targeted Antibody-Drug Conjugate to Treat Non-Small Lung Cancer (NSCLC).
A CD276-Targeted Antibody-Drug Conjugate to Treat Non-Small Lung Cancer (NSCLC).
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作者：
非小细胞肺癌 (NSCLC) 患者约占肺癌病例的 85%，通常在晚期被诊断出来。传统的手术切除和放射治疗的临床益处非常有限。本研究的目的是开发和评估用于 NSCLC 治疗的靶向疗法——抗体药物偶联物 (ADC)。具体而言，在 73 名患者肿瘤微阵列的免疫组织化学 (IHC) 染色和 8 种细胞系的蛋白质印迹分析中，评估并确认了 CD276 受体是 NSCLC 的理想表面靶标。我们的抗 CD276 单克隆抗体 (mAb) 与人和小鼠受体具有交叉活性，在流式细胞术、共聚焦显微镜和体内成像系统分析中表现出高表面结合、有效的药物递送和肿瘤特异性靶向。用我们的 CD276 mAb 和有效负载单甲基 auristatin F (MMAF) 构建的 ADC 对多种细胞系均表现出高抗 NSCLC 细胞毒性，并且在免疫功能低下和免疫功能正常的 NSCLC 异种移植小鼠模型中均表现出有效的抗肿瘤功效。简短的机制研究揭示了肿瘤微环境中细胞增殖抑制和免疫细胞重新激活的整合。毒性研究未检测到脱靶免疫毒性或外周毒性。总而言之，这项研究表明抗 CD276 ADC 可能是 NSCLC 治疗的有希望的候选者。
Non-small cell lung cancer (NSCLC) patients, accounting for approximately 85% of lung cancer cases, are usually diagnosed in advanced stages. Traditional surgical resection and radiotherapy have very limited clinical benefits. The objective of this study was to develop and evaluate a targeted therapy, antibody-drug conjugate (ADC), for NSCLC treatment. Specifically, the CD276 receptor was evaluated and confirmed as an ideal surface target of NSCLC in the immunohistochemistry (IHC) staining of seventy-three patient tumor microarrays and western blotting analysis of eight cell lines. Our anti-CD276 monoclonal antibody (mAb) with cross-activity to both human and mouse receptors showed high surface binding, effective drug delivery and tumor-specific targeting in flow cytometry, confocal microscopy, and in vivo imaging system analysis. The ADC constructed with our CD276 mAb and payload monomethyl auristatin F (MMAF) showed high anti-NSCLC cytotoxicity to multiple lines and effective anti-tumor efficacy in both immunocompromised and immunocompetent NSCLC xenograft mouse models. The brief mechanism study revealed the integration of cell proliferation inhibition and immune cell reactivation in tumor microenvironments. The toxicity study did not detect off-target immune toxicity or peripheral toxicity. Altogether, this study suggested that anti-CD276 ADC could be a promising candidate for NSCLC treatment.
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影响因子：
22.7
作者：
Lehtiö J;Arslan T;Siavelis I;Pan Y;Socciarelli F;Berkovska O;Umer HM;Mermelekas G;Pirmoradian M;Jönsson M;Brunnström H;Brustugun OT;Purohit KP;Cunningham R;Foroughi Asl H;Isaksson S;Arbajian E;Aine M;Karlsson A;Kotevska M;Gram Hansen C;Drageset Haakensen V;Helland Å;Tamborero D;Johansson HJ;Branca RM;Planck M;Staaf J;Orre LM
通讯作者：
Orre LM
影响因子：
3.7
作者：
Ou J;Si Y;Goh K;Yasui N;Guo Y;Song J;Wang L;Jaskula-Sztul R;Fan J;Zhou L;Liu R;Liu X
通讯作者：
Liu X
通过 CD276 靶向光动力消融肿瘤细胞和肿瘤脉管系统增强抗 PD-1/PD-L1 免疫检查点抑制性癌症治疗
影响因子：
4.9
作者：
Bao, Rui;Wang, Yanpu;Liu, Zhaofei
通讯作者：
Liu, Zhaofei
HER2-突变转移性非小细胞肺癌患者的曲妥珠单抗Deruxtecan：随机，II期Destiny destiny-Lung02试验的主要结果。
DOI：
10.1200/jco.23.01361
发表时间：
2023-11-01
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
通讯作者：
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影响因子：
4.7
作者：
Chen K;Si Y;Guan JS;Zhou Z;Kim S;Kim T;Shan L;Willey CD;Zhou L;Liu X
通讯作者：
Liu X