Delivery of CD47-SIRPα checkpoint blocker by BCMA-directed UCAR-T cells enhances antitumor efficacy in multiple myeloma
Copyright © 2024 Elsevier B.V. All rights reserved..
In the treatment of relapsed or refractory multiple myeloma patients, BCMA-directed autologous CAR-T cells have showed excellent anti-tumor activity. However, their widespread application is limited due to the arguably cost and time-consuming. Multiple myeloma cells highly expressed CD47 molecule and interact with the SIRPα ligand on the surface of macrophages, in which evade the clearance of macrophages through the activation of "don't eat me" signal. In this study, a BCMA-directed universal CAR-T cells, BC404-UCART, secreting a CD47-SIRPα blocker was developed using CRISPR/Cas9 gene-editing system. BC404-UCART cells significantly inhibited tumor growth and prolonged the survival of mice in the xenograft model. The anti-tumor activity of BC404-UCART cells was achieved via two mechanisms, on the one hand, the UCAR-T cells directly killed tumor cells, on the other hand, the BC404-UCART cells enhanced the phagocytosis of macrophages by secreting anti-CD47 nanobody hu404-hfc fusion that blocked the "don't eat me" signal between macrophages and tumor cells, which provides a potential strategy for the development of novel "off-the-shelf" cellular immunotherapies for the treatment of multiple myeloma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:585 |
|---|---|
| Enthalten in: |
Cancer letters - 585(2024) vom: 31. März, Seite 216660 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lu, Qizhong [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antigens, Differentiation |
|---|
| Anmerkungen: |
Date Completed 05.03.2024 Date Revised 05.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.canlet.2024.216660 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367572281 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367572281 | ||
| 003 | DE-627 | ||
| 005 | 20240305232236.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240125s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.canlet.2024.216660 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1317.xml |
| 035 | |a (DE-627)NLM367572281 | ||
| 035 | |a (NLM)38266806 | ||
| 035 | |a (PII)S0304-3835(24)00054-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lu, Qizhong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Delivery of CD47-SIRPα checkpoint blocker by BCMA-directed UCAR-T cells enhances antitumor efficacy in multiple myeloma |
| 264 | 1 | |c 2024 | |
| 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 05.03.2024 | ||
| 500 | |a Date Revised 05.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a In the treatment of relapsed or refractory multiple myeloma patients, BCMA-directed autologous CAR-T cells have showed excellent anti-tumor activity. However, their widespread application is limited due to the arguably cost and time-consuming. Multiple myeloma cells highly expressed CD47 molecule and interact with the SIRPα ligand on the surface of macrophages, in which evade the clearance of macrophages through the activation of "don't eat me" signal. In this study, a BCMA-directed universal CAR-T cells, BC404-UCART, secreting a CD47-SIRPα blocker was developed using CRISPR/Cas9 gene-editing system. BC404-UCART cells significantly inhibited tumor growth and prolonged the survival of mice in the xenograft model. The anti-tumor activity of BC404-UCART cells was achieved via two mechanisms, on the one hand, the UCAR-T cells directly killed tumor cells, on the other hand, the BC404-UCART cells enhanced the phagocytosis of macrophages by secreting anti-CD47 nanobody hu404-hfc fusion that blocked the "don't eat me" signal between macrophages and tumor cells, which provides a potential strategy for the development of novel "off-the-shelf" cellular immunotherapies for the treatment of multiple myeloma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chimeric antigen receptor | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a Multiple myeloma | |
| 650 | 4 | |a Nanobody | |
| 650 | 7 | |a B-Cell Maturation Antigen |2 NLM | |
| 650 | 7 | |a CD47 Antigen |2 NLM | |
| 650 | 7 | |a Receptors, Immunologic |2 NLM | |
| 650 | 7 | |a Antigens, Differentiation |2 NLM | |
| 650 | 7 | |a CD47 protein, human |2 NLM | |
| 700 | 1 | |a Yang, Donghui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hexian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Zhixiong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zongliang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yongdong |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Nian |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zeng |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Aiping |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer letters |d 1976 |g 585(2024) vom: 31. März, Seite 216660 |w (DE-627)NLM000147273 |x 1872-7980 |7 nnns |
| 773 | 1 | 8 | |g volume:585 |g year:2024 |g day:31 |g month:03 |g pages:216660 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.canlet.2024.216660 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 585 |j 2024 |b 31 |c 03 |h 216660 | ||