Development of OX40 agonists for canine cancer immunotherapy.
Development of OX40 agonists for canine cancer immunotherapy.
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DOI：
10.1016/j.isci.2022.105158
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发表时间：
2022-10-21
期刊：
影响因子：
5.8
通讯作者：
Sandey, Maninder
中科院分区：
文献类型：
--
作者：
Ruiz, Damien;Haynes, Chloe;Marable, Jonathan;Pundkar, Chetan;Nance, Rebecca L.;Bedi, Deepa;Agarwal, Payal;Suryawanshi, Amol S.;Mishra, Amarjit;Smith, Bruce F.;Sandey, Maninder
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益处。癌症也是导致宠物狗死亡的最常见原因之一。因此，靶向类似信号通路的犬特异性免疫疗法可以为犬癌症患者提供更好的治疗选择。在这里，我们描述了两种犬特异性抗OX 40激动剂激活OX 40信号的开发和表征。我们发现，犬OX 40，像人OX 40，不表达的静息T细胞，其表达显着增加犬CD 4 T细胞和Tcells刺激后与刀豆球蛋白A（Con-A）。在犬骨肉瘤患者中，cOX 40也在肿瘤浸润淋巴细胞（TIL）上表达。犬特异性OX 40激动剂通过增加IFN-γ表达强烈激活cPBMC，并且不需要Fc受体介导的交联来进行OX 40激动。总之，这些结果表明，cFcOX 40 L蛋白是有效的OX 40激动剂，并有可能增强犬癌症患者的抗肿瘤免疫力。犬FcOX 40 L重组蛋白作为有效的OX 40激动剂cFcOX 40 L诱导活化cPBMC的NF-κB信号传导和IFN-γ分泌cOX 40在犬骨肉瘤（OS）中的TIL上以高水平表达生物科学;系统生物学;癌症系统生物学;癌症
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. Canine FcOX40L recombinant proteins act as potent OX40 agonists cFcOX40L induces NF-κB signaling and IFN-γ secretion from activated cPBMCs cOX40 is expressed at high levels on TILs in canine osteosarcoma (OS) Biological sciences; Systems biology; Cancer systems biology; Cancer
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T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
PD-1和PD-L1检查点信号传导抑制癌症免疫疗法：机制，组合和临床结果。
影响因子：
5.6
作者：
Alsaab HO;Sau S;Alzhrani R;Tatiparti K;Bhise K;Kashaw SK;Iyer AK
通讯作者：
Iyer AK
影响因子：
4.6
作者：
Marable J;Ruiz D;Jaiswal AK;Bhattacharya R;Pantazes R;Agarwal P;Suryawanshi AS;Bedi D;Mishra A;Smith BF;Sandey M
通讯作者：
Sandey M
影响因子：
11.5
作者：
Gutierrez, Martin;Moreno, Victor;Melero, Ignacio
通讯作者：
Melero, Ignacio
DOI：
10.1084/jem.20120532
发表时间：
2012-10-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hirschhorn-Cymerman D;Budhu S;Kitano S;Liu C;Zhao F;Zhong H;Lesokhin AM;Avogadri-Connors F;Yuan J;Li Y;Houghton AN;Merghoub T;Wolchok JD
通讯作者：
Wolchok JD