Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific antibodies against B-cell acute lymphoblastic leukemia:targeted immunotherapy for acute lymphoblastic leukemia

• 作者: Sisi Wang Lijun Peng Wenqian Xu Yuebo Zhou Ziyan Zhu Yushan Kong Stewart Leung Jin Wang Xiaoqiang Yan Jian-Qing Mi
• 来源期刊: 医学前沿
• 年，卷（期）: 2022,（1）
• 所属期刊栏目: Research Articles
• 页码范围: 139-149
• 页数: 11页
• 语种: 英文

摘要

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.However,several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight,and thus its clinical use is limited.Furthermore,multiple trials have shown that approximately 30％of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells.Here,we design and characterize two novel antibodies,A-319 and A-2019.Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures,and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function.Our in vitro,ex vivo,and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells,enhancing T-cell function,mediating B-cell depletion,and eventually inhibiting tumor growth in Raji xenograft models.The two molecules are complementary in terms of efficacy and specificity profile.The activity of A-319 demonstrated superior to that of A-2019,whereas A-2019 has an additional capability to target CD20 in cells missing CD19,suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.