Canadian Blood Services, Toronto, ON, Canada.
Blood. 2011 Jan 20;117(3):971-4. doi: 10.1182/blood-2010-05-280115. Epub 2010 Nov 2.
To explore the potential for monoclonal antibodies as a treatment for immune thrombocytopenia (ITP) and to further explore their mechanisms of action, we tested 8 monoclonal CD44 antibodies in murine ITP and found 4 antibodies that could successfully ameliorate ITP; 2 of these antibodies function at a full 3-log fold lower dosage compared with IVIg. Further characterization of the 2 most successful antibodies (5035-41.1D and KM114) demonstrated that, similar to IVIg: (1) the presence of the inhibitory IgG receptor FcγRIIB was required for their ameliorative function, (2) complement-deficient mice responded to anti-CD44 treatment, and (3) human transgenic FcγRIIA-expressing mice also responded to the CD44 therapeutic modality. Dissimilar to IVIg, the Fc portion of the CD44 antibody was not required. These data demonstrate that CD44 antibodies can function therapeutically in murine ITP and that they could potentially provide a very-low-dose recombinant therapy for the amelioration of human ITP.
为了探索单克隆抗体作为治疗免疫性血小板减少症（ITP）的可能性，并进一步探索其作用机制，我们在小鼠 ITP 中测试了 8 种单克隆 CD44 抗体，发现有 4 种抗体可以成功改善 ITP；其中 2 种抗体的作用剂量比 IVIg 低 3 个对数倍。对 2 种最成功的抗体（5035-41.1D 和 KM114）的进一步表征表明，与 IVIg 相似：（1）抑制性 IgG 受体 FcγRIIB 的存在是其改善作用所必需的，（2）补体缺陷小鼠对抗 CD44 治疗有反应，（3）人源转基因 FcγRIIA 表达小鼠也对 CD44 治疗方式有反应。与 IVIg 不同，CD44 抗体的 Fc 部分不是必需的。这些数据表明，CD44 抗体可在小鼠 ITP 中发挥治疗作用，并且它们可能为改善人类 ITP 提供一种非常低剂量的重组治疗方法。
