Department of Immunology and Oncology, Centro Nacional de Biotecnologia (CNB-CSIC), Madrid, Spain.
Protein Tools Unit, Centro Nacional de Biotecnologia (CNB-CSIC), Madrid, Spain.
Front Immunol. 2018 Jan 29;9:77. doi: 10.3389/fimmu.2018.00077. eCollection 2018.
CCR9 is as an interesting target for the treatment of human CCR9-T cell acute lymphoblastic leukemia, since its expression is limited to immature cells in the thymus, infiltrating leukocytes in the small intestine and a small fraction of mature circulating T lymphocytes. 92R, a new mouse mAb (IgG2a isotype), was raised using the A-isoform of hCCR9 as immunogen. Its initial characterization demonstrates that binds with high affinity to the CCR9 N-terminal domain, competing with the previously described 91R mAb for receptor binding. 92R inhibits human CCR9 tumor growth in T and B-cell deficient Rag2 mice. assays suggested complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity as possible mechanisms of action. Unexpectedly, 92R strongly inhibited tumor growth also in a model with compromised NK and complement activities, suggesting that other mechanisms, including phagocytosis or apoptosis, might also be playing a role on 92R-mediated tumor elimination. Taken together, these data contribute to strengthen the hypothesis of the immune system's opportunistic nature.
CCR9 是治疗人类 CCR9-T 细胞急性淋巴细胞白血病的一个有趣靶点，因为它的表达仅限于胸腺中的未成熟细胞、小肠浸润的白细胞和一小部分成熟的循环 T 淋巴细胞。92R 是一种新的小鼠 mAb（IgG2a 同种型），使用 hCCR9 的 A 异构体作为免疫原制备。其初步特征表明，它与 CCR9 N 端结构域高亲和力结合，与先前描述的 91R mAb 竞争受体结合。92R 抑制 T 和 B 细胞缺陷 Rag2 小鼠中的人 CCR9 肿瘤生长。杀伤试验表明补体依赖性细胞毒性和抗体依赖性细胞介导的细胞毒性可能是作用机制。出乎意料的是，92R 也能强烈抑制 NK 和补体活性受损模型中的肿瘤生长，这表明其他机制，包括吞噬作用或细胞凋亡，也可能在 92R 介导的肿瘤消除中发挥作用。综上所述，这些数据有助于加强免疫系统机会性本质的假说。
