CD3型
双特异性抗体
抗体
CD19
癌症研究
Blinatumoab公司
医学
T细胞
免疫学
抗原
单克隆抗体
免疫系统
CD8型
作者
Ze Tian,Chunhua Shi,Guojun Yang,Jason K. Allen,Qi Shi,Amin AI-Shami,Jill Wardell Olson,Melinda Smith,Qing Chang,Jasbir Kaur,Junping You,Timothy Lofton,Michelle A. González,Qi Zhang,Dongxing Zha,Sarah K. Tasian,Nitin Jain,Marina Konopleva,Timothy Heffernan,Jeffrey J. Molldrem
出处
期刊:Leukemia
[Springer Nature]
日期:2023-08-26
卷期号:37 (10): 2006-2016
标识
DOI:10.1038/s41375-023-02010-y
摘要
Patients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-year survival rate as low as 20%. While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response. Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19. Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR. In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR. Further, 1B7/CD3 was shown to induce potent T cell activation and tumor lytic activity in both cell lines and primary B-ALL patient samples. Using humanized cell- or patient-derived xenograft models, 1B7/CD3 treatment was shown to trigger dose-dependent tumor remission or growth inhibition across donors as well as induce T cell activation and expansion. Pharmacokinetic studies in murine models revealed 1B7/CD3 to exhibit a prolonged half-life. Finally, toxicology studies using cynomolgus monkeys found that the maximum tolerated dose of 1B7/CD3 was ≤1 mg/kg. Overall, our preclinical data provide the framework for the clinical evaluation of 1B7/CD3 in patients with CRLF2-rearranged B-ALL.
科研通智能强力驱动
Strongly Powered by AbleSci AI