Min Jin Young, Ko Tae Kyung, Kim Hye Min, Jung Hae Won, Yim Cha Ok, Han Eun Hee
Biopharmaceutical Research Center, Ochang Institute of Biological and Environmental Science, Korea Basic Science Institute (KBSI), Cheongju, South Korea.
TSBIO ALL Co., Ltd, Seoul, South Korea.
Immunol Cell Biol. 2025 Aug;103(7):664-682. doi: 10.1111/imcb.70038. Epub 2025 Jun 18.
In this study, we employed a coculture system to expand natural killer (NK) cells ex vivo from healthy donors and patients with breast cancer and investigated their surface marker expression. We further analyzed the activation markers of primary expanded NK cells on Day 13 using cytokine arrays and dimensionality reduction techniques. Cytokine profiles were observed on Days 0, 6 and 13 (TS-NK). To validate the anticancer activity of the expanded NK cells, we conducted lactate dehydrogenase assays against the hematologic cancer cell line K562 using cells from 10 donors (five patients with cancer and five healthy individuals). Additionally, we examined the antibody-dependent cellular cytotoxicity (ADCC) of differentiated NK cells cocultured with SK-BR-3 cells in the presence of the HER2-targeting monoclonal antibodies, trastuzumab and pertuzumab. Our findings demonstrate the stable expansion of NK cells from donor peripheral blood mononuclear cells and their potent anticancer effects and ADCC against both hematologic and solid tumors, highlighting their potential as a versatile therapeutic approach in oncology.
在本研究中，我们采用共培养系统从健康供体和乳腺癌患者体内体外扩增自然杀伤（NK）细胞，并研究其表面标志物表达。我们进一步使用细胞因子阵列和降维技术分析了第13天原代扩增NK细胞的激活标志物。在第0、6和13天观察细胞因子谱（TS-NK）。为了验证扩增的NK细胞的抗癌活性，我们使用来自10名供体（5名癌症患者和5名健康个体）的细胞对血液癌细胞系K562进行了乳酸脱氢酶测定。此外，我们在HER2靶向单克隆抗体曲妥珠单抗和帕妥珠单抗存在的情况下，检测了与SK-BR-3细胞共培养的分化NK细胞的抗体依赖性细胞毒性（ADCC）。我们的研究结果表明，NK细胞可从供体外周血单个核细胞中稳定扩增，并且对血液肿瘤和实体瘤均具有强大的抗癌作用和ADCC，突出了它们作为肿瘤学中一种通用治疗方法的潜力。
