Teclistamab is an active T cell–redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma

多发性骨髓瘤 抗体 分子生物学 双特异性抗体 抗原 B细胞 细胞 T细胞 癌症研究 免疫学 生物 病毒学 单克隆抗体 免疫系统 遗传学
作者
Kodandaram Pillarisetti,Gordon Powers,Leopoldo Luistro,Alexander Babich,Eric T. Baldwin,Yingzhe Li,Xiaochun Zhang,Mark Mendonça,Nate Majewski,Rupesh Nanjunda,Diana Chin,Kathryn Packman,Yusri Elsayed,Ricardo M. Attar,François Gaudet
出处
期刊:Blood Advances [Elsevier BV]
卷期号:4 (18): 4538-4549 被引量:105
标识
DOI:10.1182/bloodadvances.2020002393
摘要

Abstract B-cell maturation antigen (BCMA), a member of the tumor necrosis factor family of receptors, is predominantly expressed on the surface of terminally differentiated B cells. BCMA is highly expressed on plasmablasts and plasma cells from multiple myeloma (MM) patient samples. We developed a BCMAxCD3 bispecific antibody (teclistamab [JNJ-64007957]) to recruit and activate T cells to kill BCMA-expressing MM cells. Teclistamab induced cytotoxicity of BCMA+ MM cell lines in vitro (H929 cells, 50% effective concentration [EC50] = 0.15 nM; MM.1R cells, EC50 = 0.06 nM; RPMI 8226 cells, EC50 = 0.45 nM) with concomitant T-cell activation (H929 cells, EC50 = 0.21 nM; MM.1R cells, EC50 = 0.1 nM; RPMI 8226 cells, EC50 = 0.28 nM) and cytokine release. This activity was further increased in the presence of a γ-secretase inhibitor (LY-411575). Teclistamab also depleted BCMA+ cells in bone marrow samples from MM patients in an ex vivo assay with an average EC50 value of 1.7 nM. Under more physiological conditions using healthy human whole blood, teclistamab mediated dose-dependent lysis of H929 cells and activation of T cells. Antitumor activity of teclistamab was also observed in 2 BCMA+ MM murine xenograft models inoculated with human T cells (tumor inhibition with H929 model and tumor regression with the RPMI 8226 model) compared with vehicle and antibody controls. The specific and potent activity of teclistamab against BCMA-expressing cells from MM cell lines, patient samples, and MM xenograft models warrant further evaluation of this bispecific antibody for the treatment of MM. Phase 1 clinical trials (monotherapy, #NCT03145181; combination therapy, #NCT04108195) are ongoing for patients with relapsed/refractory MM.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
PureKK完成签到,获得积分10
刚刚
整齐棉花糖完成签到,获得积分10
1秒前
2秒前
123完成签到 ,获得积分10
3秒前
王二饼发布了新的文献求助10
5秒前
笑点低靖雁完成签到,获得积分10
5秒前
。。。发布了新的文献求助20
8秒前
情怀应助小伙不错采纳,获得20
9秒前
。。。完成签到 ,获得积分10
13秒前
自然的小熊猫完成签到 ,获得积分10
14秒前
14秒前
Spteer完成签到,获得积分10
16秒前
上官若男应助nemo采纳,获得10
16秒前
Lee完成签到,获得积分10
17秒前
17秒前
19秒前
田様应助张某某采纳,获得10
20秒前
怕黑的擎发布了新的文献求助10
22秒前
22秒前
23秒前
李倇仪完成签到,获得积分10
24秒前
小伙不错发布了新的文献求助20
24秒前
谨慎飞丹完成签到 ,获得积分0
26秒前
nemo发布了新的文献求助10
28秒前
儒雅凡桃发布了新的文献求助10
28秒前
29秒前
可靠的冰烟完成签到,获得积分10
33秒前
大白完成签到,获得积分10
33秒前
33秒前
YoungLee完成签到,获得积分10
36秒前
HEIKU应助阿宝采纳,获得10
37秒前
42秒前
43秒前
王二饼完成签到,获得积分20
45秒前
betyby完成签到 ,获得积分10
46秒前
YOLO完成签到 ,获得积分10
46秒前
汉堡包应助一区top采纳,获得10
47秒前
上上签发布了新的文献求助10
48秒前
嘟嘟完成签到,获得积分10
49秒前
忧郁难胜完成签到,获得积分10
50秒前
高分求助中
Encyclopedia of Mathematical Physics 2nd edition 888
Introduction to Strong Mixing Conditions Volumes 1-3 500
Tip60 complex regulates eggshell formation and oviposition in the white-backed planthopper, providing effective targets for pest control 400
Optical and electric properties of monocrystalline synthetic diamond irradiated by neutrons 320
共融服務學習指南 300
Essentials of Pharmacoeconomics: Health Economics and Outcomes Research 3rd Edition. by Karen Rascati 300
Peking Blues // Liao San 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3801430
求助须知:如何正确求助?哪些是违规求助? 3347140
关于积分的说明 10332038
捐赠科研通 3063426
什么是DOI,文献DOI怎么找? 1681673
邀请新用户注册赠送积分活动 807650
科研通“疑难数据库(出版商)”最低求助积分说明 763843