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] |
---|
Links: |
---|
Themen: |
Antibodies |
---|
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 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM342505149 | ||
003 | DE-627 | ||
005 | 20231226204858.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1038/s41598-022-14523-0 |2 doi | |
028 | 5 | 2 | |a pubmed24n1141.xml |
035 | |a (DE-627)NLM342505149 | ||
035 | |a (NLM)35729339 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Zhang, Shangkun |e verfasserin |4 aut | |
245 | 1 | 4 | |a The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 23.06.2022 | ||
500 | |a Date Revised 25.08.2022 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2022. The Author(s). | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Antibodies |2 NLM | |
650 | 7 | |a Ki-1 Antigen |2 NLM | |
700 | 1 | |a Gu, Chaojiang |e verfasserin |4 aut | |
700 | 1 | |a Huang, Lifang |e verfasserin |4 aut | |
700 | 1 | |a Wu, Han |e verfasserin |4 aut | |
700 | 1 | |a Shi, Jiangzhou |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Zijian |e verfasserin |4 aut | |
700 | 1 | |a Zhou, Yong |e verfasserin |4 aut | |
700 | 1 | |a Zhou, Jingjiao |e verfasserin |4 aut | |
700 | 1 | |a Gao, Yang |e verfasserin |4 aut | |
700 | 1 | |a Liu, Jiaxing |e verfasserin |4 aut | |
700 | 1 | |a Leng, Yingqi |e verfasserin |4 aut | |
700 | 1 | |a Liu, Xiyu |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Qinxing |e verfasserin |4 aut | |
700 | 1 | |a Huang, Liang |e verfasserin |4 aut | |
700 | 1 | |a Tong, Xiqin |e verfasserin |4 aut | |
700 | 1 | |a Young, Ken H |e verfasserin |4 aut | |
700 | 1 | |a Li, Jiapeng |e verfasserin |4 aut | |
700 | 1 | |a Zhu, Haichuan |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Tongcun |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Scientific reports |d 2011 |g 12(2022), 1 vom: 21. Juni, Seite 10488 |w (DE-627)NLM215703936 |x 2045-2322 |7 nnns |
773 | 1 | 8 | |g volume:12 |g year:2022 |g number:1 |g day:21 |g month:06 |g pages:10488 |
856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41598-022-14523-0 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 12 |j 2022 |e 1 |b 21 |c 06 |h 10488 |