抗原
癌症研究
抗体
多发性骨髓瘤
骨髓
CD3型
免疫疗法
细胞毒性T细胞
抗体依赖性细胞介导的细胞毒性
医学
细胞毒性
T细胞
嵌合抗原受体
免疫学
分子生物学
化学
生物
免疫系统
体外
单克隆抗体
CD8型
生物化学
作者
Kodandaram Pillarisetti,Suzanne C. Edavettal,Mark Mendonça,Yingzhe Li,Mark A. Tornetta,Alexander Babich,Nate Majewski,Matt Husovsky,Dara Reeves,Eileen S. Walsh,Diana Chin,Leopoldo Luistro,Jocelin Joseph,Gerald C. Chu,Kathryn Packman,Shoba Shetty,Yusri Elsayed,Ricardo M. Attar,François Gaudet
出处
期刊:Blood
[American Society of Hematology]
日期:2020-04-09
卷期号:135 (15): 1232-1243
被引量:86
标识
DOI:10.1182/blood.2019003342
摘要
Abstract T-cell–mediated approaches have shown promise in myeloma treatment. However, there are currently a limited number of specific myeloma antigens that can be targeted, and multiple myeloma (MM) remains an incurable disease. G-protein–coupled receptor class 5 member D (GPRC5D) is expressed in MM and smoldering MM patient plasma cells. Here, we demonstrate that GPRC5D protein is present on the surface of MM cells and describe JNJ-64407564, a GPRC5DxCD3 bispecific antibody that recruits CD3+ T cells to GPRC5D+ MM cells and induces killing of GPRC5D+ cells. In vitro, JNJ-64407564 induced specific cytotoxicity of GPRC5D+ cells with concomitant T-cell activation and also killed plasma cells in MM patient samples ex vivo. JNJ-64407564 can recruit T cells and induce tumor regression in GPRC5D+ MM murine models, which coincide with T-cell infiltration at the tumor site. This antibody is also able to induce cytotoxicity of patient primary MM cells from bone marrow, which is the natural site of this disease. GPRC5D is a promising surface antigen for MM immunotherapy, and JNJ-64407564 is currently being evaluated in a phase 1 clinical trial in patients with relapsed or refractory MM (NCT03399799).
科研通智能强力驱动
Strongly Powered by AbleSci AI