Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype.
Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype.
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DOI：
10.1182/blood.v73.6.1431.1431
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发表时间：
1989-05
期刊：
影响因子：
20.3
通讯作者：
Martin J. S. Dyer;Geoff Hale;F. Hayhoe;H. Waldmann
中科院分区：
文献类型：
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作者：
Martin J. S. Dyer;Geoff Hale;F. Hayhoe;H. Waldmann
CAMPATH-1抗体家族识别几乎所有人淋巴细胞上表达的丰富糖蛋白。具有这种特异性的所有大鼠IgM和IgG抗体都能与人补体裂解，但只有IgG 2b在抗体依赖性细胞介导的细胞毒性（ADCC）中具有活性。我们比较了IgM，IgG 2a和IgG 2b在体内消耗淋巴细胞的能力，在两个患者的幼淋巴细胞转化的B细胞慢性淋巴细胞白血病（CLL）。IgM（CAMPATH-1 M）在消耗补体的情况下产生血液淋巴细胞的一过性耗竭，但对实体肿块或骨髓无影响。在IgG 2a（YTH 34.5）中观察到类似的血液淋巴细胞一过性耗竭。相比之下，IgG 2b（CAMPATH-1G）产生了血液和骨髓中淋巴细胞的持久消耗和脾肿大的改善，但补体水平没有可检测到的变化。这些差异可能反映了Fc受体结合对体内靶细胞有效清除的重要性。我们治疗了另外16名患有各种淋巴系统恶性肿瘤的患者，并注意到对血液淋巴细胞、骨髓浸润和脾肿大的一致影响。在该剂量水平下，受累淋巴结或淋巴结肿块的改善相对较小。尽管如此，与其他单克隆抗体（MoAb）相比，CAMPATH-1G的体内淋巴溶解能力非常强，可能在淋巴恶性肿瘤的治疗中以及作为免疫抑制剂方面有应用。
The CAMPATH-1 family of antibodies recognize an abundant glycoprotein expressed on virtually all human lymphocytes. All rat IgM and IgG antibodies of this specificity are lytic with human complement, but only IgG2b is active in antibody-dependent cell-mediated cytotoxicity (ADCC). We compared the ability of IgM, IgG2a, and IgG2b to deplete lymphocytes in vivo in two patients with prolymphocytic transformation of B-cell chronic lymphocytic leukemia (CLL). The IgM (CAMPATH-1M) produced transient depletion of blood lymphocytes with consumption of complement but had no effect on solid masses or bone marrow. Similar transient depletion of blood lymphocytes was noted with the IgG2a (YTH34.5). In contrast, the IgG2b (CAMPATH-1G) produced long-lasting depletion of lymphocytes from blood and marrow and improvement in splenomegaly but no detectable changes in complement levels. These differences probably reflect the importance of Fc receptor binding for effective clearance of target cells in vivo. We treated 16 more patients with a variety of lymphoid malignancies and noted consistent effects on blood lymphocytes, marrow infiltration, and splenomegaly. At this dose level, there was comparatively little improvement in affected lymph nodes or extranodal masses. Nevertheless, the in vivo lympholytic ability of CAMPATH-1G is very potent as compared with other monoclonal antibodies (MoAbs) and may have applications in therapy of lymphoid malignancies and as an immunosuppressive agent.