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.
10.1007/s11684-021-0835-8
- Author:
Sisi WANG
1
;
Lijun PENG
1
;
Wenqian XU
1
;
Yuebo ZHOU
1
;
Ziyan ZHU
2
;
Yushan KONG
3
;
Stewart LEUNG
3
;
Jin WANG
4
;
Xiaoqiang YAN
5
;
Jian-Qing MI
6
Author Information
1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
2. Shanghai Blood Center, Shanghai, 200051, China.
3. Generon Biomed, Shanghai, 201210, China.
4. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. jinwang@shsmu.edu.cn.
5. Generon Biomed, Shanghai, 201210, China. yxq3000@icloud.com.
6. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. jianqingmi@shsmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
B-cell acute lymphoblastic leukemia;
CD19;
CD20;
bispecific antibody;
trispecific antibody
- MeSH:
Antigens, CD19/therapeutic use*;
Antineoplastic Agents/pharmacology*;
Humans;
Immunotherapy;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*;
T-Lymphocytes
- From:
Frontiers of Medicine
2022;16(1):139-149
- CountryChina
- Language:English
-
Abstract:
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.
