近年来,肿瘤仍然是恶性疾病发病率和死亡率居高不下的主要原因之一,许多机制涉及抑制能够影响肿瘤进展的免疫细胞,有助于肿瘤的治疗和预防。2022年6月美国肿瘤协会(ASCO)报告显示Nadunolimab在治疗胰腺癌(PDAC)患者的1/2a期试验中取得积极进展,并计划在PDAC中进行联合化疗的2/3期临床试验[1]。Nadunolimab(CAN04)是一种完全人源化的IgG1抗体,以IL-1RAcP为靶点,可以阻断IL-1α和IL-1β信号传导。Nadunolimab这一肿瘤领域新突破,也预示着IL-1RAcP作为肿瘤治疗靶点的无限潜能。
来源:ASCO 2022
IL-1RAcP介导肿瘤反应的潜在机制
IL-1RAcP可以通过募集信号介质启动炎症信号通路,而该炎症信号在肿瘤细胞的多个基因亚型中持续过度表达,使得IL-1RAcP已成为一种新的治疗靶点[3,4]。此外,Zarezadeh et.al (2022) 研究指出,IL-1RAcP异常信号在自身免疫、肥胖、银屑病、1型糖尿病、子宫内膜异位症、子痫前期和阿尔茨海默病等慢性炎症性疾病的发病机制中同样起着重要作用。Trad et.al (2022)发现与常见的潜在急性髓细胞白血病(AML)靶点相比,IL-1RAcP无疑是AML中一个有前景的治疗靶点。综上,未来对IL-1RAcP的靶向研究可以使我们更好地了解这些疾病的潜在机制。
IL-1RAcP的不同亚型及其与IL-1超家族蛋白的相互作用
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✿ 经电泳(SDS-PAGE)验证,Human IL-1RAcP , His, Avitag (Cat. No. ILP-H5225) 蛋白纯度高于95%。
Human IL-1RAcP, His Tag (Cat. No. ILP-H5225) on SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%.
✿ 经SEC-MALS验证,Biotinylated Human IL-1RAcP, His, Avitag (Cat. No. ILP-H82E5)蛋白纯度/结构均一性高于90%。
The purity of Biotinylated Human IL-1RAcP, His, Avitag (Cat. No. ILP-H82E5) is more than 90% and the molecular weight of this protein is around 50-68 kDa verified by SEC-MALS.
✿ 经ELISA验证,IL-1RL1(Cat. No. IL1-H5250)可与IL-33(Cat. No. IL3-H52H7)特异性结合,线性区间为5-40 ng/mL。
Immobilized Human IL-1RL1, Fc Tag (Cat. No. IL1-H5250) at 5 μg/mL (100 μL/well) can bind Human IL-33, His Tag (Cat. No. IL3-H52H7) with a linear range of 5-40 ng/mL (QC tested).
✿ 经BLI验证, IL-1RL1(Cat. No. IL1-H5250)可与 IL-33 (Cat. No. IL3-H82H5) 特异性结合,亲和力常数为1.81 nM。
Loaded Human IL-1RL1, Fc Tag (Cat. No. IL1-H5250) on Protein A Biosensor, can bind with Biotinylated Human IL-33, His,Avitag (Cat. No. IL3-H82H5) an affinity constant of 1.81 nM as determined in BLI assay (ForteBio Octet Red96e) (Routinely tested).
参考文献:
1. Rydberg Millrud, C., Deronic, A., Grönberg, C., Jaensson Gyllenbäck, E., von Wachenfeldt, K., Forsberg, G., & Liberg, D. (2022). Blockade of IL-1α and IL-1β signaling by the anti-IL1RAP antibody nadunolimab (CAN04) mediates synergistic anti-tumor efficacy with chemotherapy. Cancer Immunology, Immunotherapy, 1-12. https://doi.org/10.1007/s00262-022-03277-3.
2. Lv, Q., Xia, Q., Li, A., & Wang, Z. (2021). The potential role of IL1RAP on tumor microenvironment-related inflammatory factors in stomach adenocarcinoma. Technology in cancer research & treatment, 20, 1533033821995282.https://doi.org/10.1177/1533033821995282.
3. Zarezadeh Mehrabadi, A., Aghamohamadi, N., Khoshmirsafa, M., Aghamajidi, A., Pilehforoshha, M., Massoumi, R., & Falak, R. (2022). The roles of interleukin‐1 receptor accessory protein in certain inflammatory conditions. Immunology, 166(1), 38-46. https://doi.org/10.1111/imm.13462.
4. Trad, R., Warda, W., Alcazer, V., da Rocha, M. N., Berceanu, A., Nicod, C., ... & Ferrand, C. (2022). Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia. Journal for Immunotherapy of Cancer, 10(7). https://doi.org/10.1136/jitc-2021-004222.
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