Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma

细胞毒性T细胞 癌症研究 免疫疗法 生物 T细胞 移植 免疫学
作者
Siler H Panowski,Surabhi Srinivasan,Nguyen Tan,Silvia K. Tacheva-Grigorova,Bryan Smith,Yvonne Mak,Hongxiu Ning,Jonathan Villanueva,Dinali Wijewarnasuriya,Shanshan Lang,Zea Melton,Adit Ghosh,Mathilde Dusseaux,Roman Galetto,Jonathan R. Heyen,Tao Sai,Thomas Van Blarcom,Javier Chaparro-Riggers,Barbra Sasu
出处
期刊:Cancer Research [American Association for Cancer Research]
标识
DOI:10.1158/0008-5472.can-21-2931
摘要

Abstract CD70 is highly expressed in renal cell carcinoma (RCC), with limited expression in normal tissue, making it an attractive CAR T target for an immunogenic solid tumor indication. Here we generated and characterized a panel of anti-CD70 scFv-based CAR T cells. Despite the expression of CD70 on T cells, production of CAR T from a subset of scFvs with potent in vitro activity was achieved. Expression of CD70 CARs masked CD70 detection in cis and provide protection from CD70 CAR T-mediated fratricide. Two distinct classes of CAR T cells were identified with differing memory phenotype, activation status, and cytotoxic activity. Epitope mapping revealed that the two classes of CARs bind unique regions of CD70. CD70 CAR T cells displayed robust antitumor activity against RCC cell lines and patient-derived xenograft mouse models. Tissue cross-reactivity studies identified membrane staining in lymphocytes, thus matching the known expression pattern of CD70. In a cynomolgus monkey CD3-CD70 bispecific toxicity study, expected findings related to T cell activation and elimination of CD70-expressing cells were observed, including cytokine release and loss of cellularity in lymphoid tissues. Lastly, highly functional CD70 allogeneic CAR T cells were produced at large scale through elimination of the T cell receptor by TALEN-based gene editing. Taken together, these efficacy and safety data support the evaluation of CD70 CAR T cells for the treatment of RCC and has led to the advancement of an allogeneic CD70 CAR T candidate into phase I clinical trials.
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
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
3秒前
SAINT发布了新的文献求助10
4秒前
Ava应助唯心如意采纳,获得10
6秒前
桐桐应助科研通管家采纳,获得10
6秒前
科研通AI2S应助科研通管家采纳,获得10
6秒前
慕青应助科研通管家采纳,获得10
6秒前
科研通AI2S应助科研通管家采纳,获得10
6秒前
pany应助科研通管家采纳,获得10
6秒前
6秒前
Akim应助科研通管家采纳,获得10
6秒前
6秒前
小马甲应助科研通管家采纳,获得10
6秒前
吴龙完成签到,获得积分10
7秒前
江子川发布了新的文献求助10
8秒前
赘婿应助阳光傲菡采纳,获得10
9秒前
在水一方应助禹映安采纳,获得10
17秒前
小马甲应助kk采纳,获得10
19秒前
19秒前
冷傲的迎南完成签到 ,获得积分10
20秒前
21秒前
21秒前
江大橘完成签到,获得积分10
21秒前
22秒前
Ava应助笑儿采纳,获得10
23秒前
GDaisy完成签到,获得积分20
24秒前
满满阳光发布了新的文献求助30
25秒前
25秒前
26秒前
聪慧代天发布了新的文献求助10
26秒前
29秒前
29秒前
禹映安发布了新的文献求助10
30秒前
满满阳光完成签到,获得积分10
31秒前
SAINT发布了新的文献求助10
33秒前
song发布了新的文献求助10
33秒前
34秒前
34秒前
34秒前
kk发布了新的文献求助10
34秒前
36秒前
高分求助中
The body in description of emotion: cross-linguistic studies 1000
Earth System Geophysics 1000
Co-opetition under Endogenous Bargaining Power 666
Medicina di laboratorio. Logica e patologia clinica 600
Sarcolestes leedsi Lydekker, an ankylosaurian dinosaur from the Middle Jurassic of England 500
《关于整治突出dupin问题的实施意见》(厅字〔2019〕52号) 500
Language injustice and social equity in EMI policies in China 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3212662
求助须知:如何正确求助?哪些是违规求助? 2861635
关于积分的说明 8129713
捐赠科研通 2527610
什么是DOI,文献DOI怎么找? 1361352
科研通“疑难数据库(出版商)”最低求助积分说明 643451
邀请新用户注册赠送积分活动 615789