The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity

© 2022. The Author(s)..

CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Scientific reports - 12(2022), 1 vom: 21. Juni, Seite 10488

Sprache:

Englisch

Beteiligte Personen:

Zhang, Shangkun [VerfasserIn]
Gu, Chaojiang [VerfasserIn]
Huang, Lifang [VerfasserIn]
Wu, Han [VerfasserIn]
Shi, Jiangzhou [VerfasserIn]
Zhang, Zijian [VerfasserIn]
Zhou, Yong [VerfasserIn]
Zhou, Jingjiao [VerfasserIn]
Gao, Yang [VerfasserIn]
Liu, Jiaxing [VerfasserIn]
Leng, Yingqi [VerfasserIn]
Liu, Xiyu [VerfasserIn]
Zhang, Qinxing [VerfasserIn]
Huang, Liang [VerfasserIn]
Tong, Xiqin [VerfasserIn]
Young, Ken H [VerfasserIn]
Li, Jiapeng [VerfasserIn]
Zhu, Haichuan [VerfasserIn]
Zhang, Tongcun [VerfasserIn]

Links:

Volltext

Themen:

Antibodies
Journal Article
Ki-1 Antigen
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 23.06.2022

Date Revised 25.08.2022

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-022-14523-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM342505149