Cited by 15CAR-T cell therapy researchPhagocytosis and Immune RegulationMultiple Myeloma Research and Treatments

Delivery of CD47-SIRPα checkpoint blocker by BCMA-directed UCAR-T cells enhances antitumor efficacy in multiple myeloma

Lu, Qizhong, Yang, Donghui, Li, Hexian, Zhu, Zhixiong, Zhang, Zongliang, Chen, Yongdong, Yang, Nian, Li, Jia +3 more·2024·Cancer Letters

Abstract

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.

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Crossref · 10.1016/j.canlet.2024.216660

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  • BC404-UCART cells were shown to significantly inhibit the growth of MM tumor cells and prolong the survival of mice in a xenograft model.

    “BC404-UCART cells were shown to significantly inhibit the growth of MM tumor cells and prolong the survival of mice in a xenograft model.”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [265]

  • The use of a CD47-SIRPα blocker may enhance the efficacy of CAR-T cell therapy by overcoming immune evasion mechanisms employed by tumor cells.

    “The use of a CD47-SIRPα blocker may enhance the efficacy of CAR-T cell therapy by overcoming immune evasion mechanisms employed by tumor cells [265].”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [265]

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Authors
Lu, Q., Yang, D., Li, H., Zhu, Z., Zhang, Z., Chen, Y., Yang, N., Li, J., Wang, Z., Niu, T., & Tong, A.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Northwest A&F University (CN)
  • Sichuan University (CN)
Corresponding author
  • Niu, Ting
  • Tong, Aiping
Venue
Cancer Letters
Publisher
Elsevier BV
Published
2024-03
Volume
585
Pages
216660
ISSN
0304-3835 (ISSN-L)
OpenAlex
W4391116732
Cited by
15
References
75
Citations by year
2026: 3 · 2025: 8 · 2024: 4
FWCI
2.55
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Letters (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
Keywords
multiple myeloma, BCMA, universal CAR-T cells, off-the-shelf CAR-T, macrophage phagocytosis, don't eat me signal, CRISPR/Cas9 genome editing, autologous CAR T cells, relapsed/refractory multiple myeloma
MeSH terms
Animals, Antigens, Differentiation, Humans, Multiple Myeloma, Neoplasms, Phagocytosis, Receptors, Immunologic, T-Lymphocytes, Mice, CD47 Antigen, B-Cell Maturation Antigen

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