Caron P C, Scheinberg D A
Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Leuk Lymphoma. 1993;11 Suppl 2:1-6. doi: 10.3109/10428199309064254.
Leukemia is well suited for monoclonal antibody therapy due to the accessible, differentiation antigens that characterize stages of maturation. In this paper, we describe the use of radio-labeled M195, a murine IgG2a, anti-CD33 monoclonal antibody, that can be used to effectively cytoreduce AML cells in relapsed patients when tumor burden is high; or to eliminate minimal residual disease and lengthen disease-free survival in patients with APL in remission. To decrease the likelihood of immunogenicity, a humanized IgG1 version of M195 was constructed that demonstrated a higher avidity and improved effector function than the parent murine antibody. Preliminary results of the first trial in AML using a humanized antibody showed specific bone marrow targeting without an immunogenic response.
白血病非常适合单克隆抗体治疗,因为其具有易于识别的、可表征成熟阶段的分化抗原。在本文中,我们描述了放射性标记的M195(一种鼠源IgG2a抗CD33单克隆抗体)的应用。当肿瘤负荷较高时,M195可有效减少复发患者的急性髓系白血病(AML)细胞;或消除急性早幼粒细胞白血病(APL)缓解期患者的微小残留病并延长无病生存期。为降低免疫原性的可能性,构建了人源化IgG1版本的M195,其亲和力高于亲本鼠源抗体,效应功能也得到了改善。使用人源化抗体进行的AML首次试验的初步结果显示,其可特异性靶向骨髓且无免疫原性反应。