Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity
Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity
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DOI：
10.1182/blood-2009-06-225979
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发表时间：
2010-06-03
期刊：
影响因子：
20.3
通讯作者：
Umana, Pablo
中科院分区：
文献类型：
--
作者：
Moessner, Ekkehard;Bruenker, Peter;Umana, Pablo
CD20是治疗b细胞恶性肿瘤的重要靶点，包括非霍奇金淋巴瘤和自身免疫性疾病。使用抗CD20单克隆抗体的b细胞消耗疗法，如利妥昔单抗，已经彻底改变了这些疾病的治疗，极大地提高了患者的总生存率。在这里，我们报道了GA101作为第一个fc工程的II型人源化抗CD20 IgG1抗体的开发。与利妥昔单抗相比，GA101增加了直接和免疫效应细胞介导的细胞毒性，并在细胞试验和全血b细胞消耗试验中表现出优越的活性。在人类淋巴瘤异种移植模型中，GA101表现出优越的抗肿瘤活性，导致肿瘤完全缓解和总生存期的增加。在非人灵长类动物中，GA101在淋巴组织（包括淋巴结和脾脏）中表现出优越的B细胞消耗活性。综上所述，这些结果为GA101作为治疗b细胞疾病的一种有希望的新疗法的发展提供了令人信服的证据。[血液。2010;115(22):4393-4402]
CD20 is an important target for the treatment of B-cell malignancies, including non-Hodgkin lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall survival in patients. Here, we report the development of GA101 as the first Fc-engineered, type II humanized IgG1 antibody against CD20. Relative to rituximab, GA101 has increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity in cellular assays and whole blood B-cell depletion assays. In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival. In nonhuman primates, GA101 demonstrates superior B cell-depleting activity in lymphoid tissue, including in lymph nodes and spleen. Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders. (Blood. 2010; 115(22): 4393-4402)