CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
开发用于犬类癌症免疫治疗的 OX40 激动剂
英文原题：Development of OX40 agonists for canine cancer immunotherapy.
查看英文原题
Development of OX40 agonists for canine cancer immunotherapy.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
癌症免疫治疗的最新突破为人类癌症患者提供了前所未有的临床获益。癌症也是宠物犬最常见的死亡原因之一。因此，针对相似信号通路的犬特异性免疫疗法可为犬癌症患者提供更好的治疗选择。在此，我们描述了两种犬特异性抗OX40激动剂的开发与表征，用于激活OX40信号。我们发现，犬OX40与人OX40一样，不表达于静息T细胞，而在刀豆蛋白A（Con-A）刺激后，其在犬CD4 T细胞和Tregs上的表达显著增加。cOX40也表达于犬骨肉瘤患者的TIL（肿瘤浸润淋巴细胞）（TILs）上。犬特异性OX40激动剂通过增加IFN-γ表达强烈激活cPBMCs，且不需要Fc受体介导的交联即可实现OX40激动作用。总之，这些结果表明cFcOX40L蛋白是强效的OX40激动剂，具有增强犬癌症患者抗肿瘤免疫的潜力。
展开英文摘要原文
Recent breakthroughs in cancer immunotherapy have provided unprecedented clinical benefits to human cancer patients. Cancer is also one of the most common causes of death in pet dogs.
Thus, canine-specific immune therapies targeting similar signaling pathways can provide better treatment options for canine cancer patients.
Here, we describe the development and characterization of two canine-specific anti-OX40 agonists to activate OX40 signaling.
We show that canine OX40, like human OX40, is not expressed on resting T cells, and its expression is markedly increased on canine CD4 T cells and Tregs after stimulation with concanavalin A (Con-A). cOX40 is also expressed on tumor-infiltrating lymphocytes (TILs) in canine osteosarcoma patients. The canine-specific OX40 agonists strongly activates cPBMCs by increasing IFN-γ expression and do not require Fc receptor-mediated cross-linking for OX40 agonism.
Together, these results suggest that cFcOX40L proteins are potent OX40 agonists and have the potential to enhance antitumor immunity in canine cancer patients.
论文信息
- 作者
- Ruiz D、Haynes C、Marable J、Pundkar C、Nance RL、Bedi D、Agarwal P、Suryawanshi AS
- 单位
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.United States
- 期刊
- iScience2022 Oct 21
- 原文标识
- PubMed 36217551 · DOI 10.1016/j.isci.2022.105158
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →