基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer.
Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer.
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在本研究中,开发了一种用于处理不同浓度的人脂肪来源间充质干细胞分泌组制剂的方案。对其分子组成进行了评估,并通过乳腺癌细胞系进行体外研究,以及在裸鼠乳腺癌模型中进行体内研究,以确定其以剂量依赖性方式抑制三阴性乳腺癌的作用。由于分泌组可能具有作为现有药物附加治疗的价值,因此评估了分泌组在单一治疗以及与紫杉醇联合治疗中的有效性。结果显示,当暴露于20 mg/ml以上的分泌组时,细胞杀伤显著,而该浓度对正常细胞无毒性。70 mg/ml的SF显示90±10%的细胞凋亡,并显著减少CD44+/CD24-、MDR1+和PDL-1+癌细胞。在体内,每日瘤内注射50 mg/ml和100 mg/ml剂量后,肿瘤未见生长,而瘤内注射生理盐水后肿瘤显著生长。该研究得出结论,SF是一种潜在的乳腺癌生物治疗药物,可初步作为其他标准治疗的附加治疗,以提供改善的疗效且无其他不良反应。
In the present study, a protocol was developed for processing of human adipose derived mesenchymal stem cell secretome formulation of varying concentration. Its molecular composition was evaluated, and its effectiveness in vitro using breast cancer cell lines, and in vivo in a nude mice breast cancer model was studied to determine its role in suppressing triple negative breast cancer in a dose dependent manner. Because the secretome could have value as an add-on therapy along with a current drug, the effectiveness of the secretome both in monotherapy and in combination therapy along with paclitaxel was evaluated.
The results showed significant cell kill when exposed to the secretome above 20 mg/ml at which concentration there was no toxicity to normal cells. 70 mg/ml of SF showed 90 10% apoptosis and significant decrease in CD44 + /CD24 - , MDR1+ and PDL-1+ cancer cells.
In vivo, the tumor showed no growth after daily intra tumor injections at 50 mg/ml and 100 mg/ml doses whereas substantial tumor growth occurred after saline intra tumor injection. The study concludes that SF is a potential biotherapeutic for breast cancer and could be used initially as an add-on therapy to other standard of care to provide improved efficacy without other adverse effects.
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