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异体 NK 细胞联合西妥昔单抗治疗头颈部鳞状细胞癌的抗肿瘤疗效临床前研究

英文原题:Preclinical investigation of anti-tumor efficacy of allogeneic natural killer cells combined with cetuximab for head and neck squamous cell carcinoma.

PubMed 2025/03/10(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

研究概要

这些发现表明,同种异体NK细胞联合西妥昔单抗可能成为HNSCC的一种潜在治疗方式,并为未来改善患者预后的临床试验提供了基础。

中文摘要

头颈部鳞状细胞癌(HNSCC)因当前治疗手段包括免疫治疗和化疗的效果有限,构成重大的治疗挑战。本研究探讨了一种新型联合疗法——使用异体自然杀伤(NK)细胞与西妥昔单抗(一种抗表皮生长因子受体单克隆抗体)——在HNSCC中增强抗肿瘤疗效的潜力。在体外实验中,将异体NK细胞与HNSCC细胞共培养以检测细胞毒性;在NOG(NOD/Shi-scid/IL-2R null)异种移植小鼠模型中进行体内实验。体外实验表明,NK细胞与西妥昔单抗联合使用时对HNSCC细胞的细胞毒性增强,这一现象归因于抗体依赖性细胞介导的细胞毒性。在体内实验中,与任一单药治疗相比,联合治疗表现出显著的抗肿瘤效果,肿瘤微环境中NK细胞浸润程度高且细胞毒性活性强。通过流式细胞术和免疫组织化学确认了NK细胞对肿瘤的浸润,突显了NK细胞(CD3 - CD56 +)存在的增加。这些发现表明,异体NK细胞与西妥昔单抗联合使用可能是HNSCC的一种潜在治疗方式,并为未来改善患者预后的临床试验提供了基础。

展开英文摘要原文

Head and neck squamous cell carcinoma (HNSCC) presents a significant therapeutic challenge because of the limited effectiveness of current treatments including immunotherapy and chemotherapy. This study investigated the potential of a novel combination therapy using allogeneic natural killer (NK) cells and cetuximab, an anti-epidermal growth factor receptor monoclonal antibody, to enhance anti-tumor efficacy in HNSCC. Allogeneic NK cells were tested against HNSCC cells in vitro and NOG (NOD/Shi-scid/IL-2R null) xenograft mouse models for cytotoxicity. In vitro assays demonstrated enhanced cytotoxicity against HNSCC cells when NK cells were combined with cetuximab, a phenomenon attributed to antibody-dependent cellular cytotoxicity. In vivo, the combination therapy exhibited a significant anti-tumor effect compared to either monotherapy, with high NK cell infiltration and cytotoxic activity in the tumor microenvironment. Tumor infiltration by NK cells was confirmed using flow cytometry and immunohistochemistry, highlighting the increased presence of NK cells (CD3 - CD56 + ). These findings suggest that combination allogeneic NK cells and cetuximab could be a potential therapeutic modality for HNSCC and provide a foundation for future clinical trials to improve patient outcomes.

论文信息

作者
Kim C、Han M、Kim G、Son W、Kim J、Gil M、Rhee YH、Sim NS
第一作者单位
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.South Korea
通讯作者单位
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. nobelg@yuhs.ac.South Korea
期刊
Cancer immunology, immunotherapy : CII2025 Mar 10
原文标识
PubMed 40063100 · DOI 10.1007/s00262-025-03959-8