Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma

Songbo Zhao; Chao Wu; Jialu Li; Yafen Li; Gangli An; Huimin Meng; Zixuan Li; Lin Yang

doi:doi:10.11648/j.jctr.20210901.12

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Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma

Songbo Zhao, Chao Wu, Jialu Li, Yafen Li, Gangli An, Huimin Meng, Zixuan Li, Lin Yang

Published in Journal of Cancer Treatment and Research (Volume 9, Issue 1)

Received: 28 April 2021 Accepted: 15 May 2021 Published: 26 May 2021

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Abstract

Multiple myeloma (MM) is a malignancy characterized by abnormal proliferation of clonal plasma cells, and it is the second most common hematologic malignancy in the world after non-Hodgkin lymphoma. In recent years, significant progress has been made in the clinical treatment of MM. In particular, certain novel drugs, such as bortezomib, lenalidomide, and carfilzomib, have greatly improved the survival rate of patients with MM. However, because of drug resistance, most MM patients eventually suffer a relapse and die of the disease. In this study, the chimeric antigen receptor-modified T cell (CAR-T cell) technology, which has achieved success in recent clinical trials for B-cell acute lymphoblastic leukemia (B-ALL), was used. In view of the high CD138 expression in MM cells and the presence of the CD138–/CD19+ phenotype in a small subset of MM cells, and based on preliminary findings of effective killing of MM cells by CD19-CAR-T cells in clinical studies, CD138- and CD19-directed CAR-T cells were constructed. Through in vitro experiments and the use of a mouse model, we proved that these two types of CAR-T cells possess strong biological activity in the specific killing of target cells, and that the concomitant use of these cells significantly enhances the killing effect in an MM mouse model.

Published in	Journal of Cancer Treatment and Research (Volume 9, Issue 1)
DOI	10.11648/j.jctr.20210901.12
Page(s)	10-21
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Multiple Myeloma, CAR-T, CD138 (syndecan-1), CD19

References

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APA Style

Songbo Zhao, Chao Wu, Jialu Li, Yafen Li, Gangli An, et al. (2021). Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma. Journal of Cancer Treatment and Research, 9(1), 10-21. https://doi.org/10.11648/j.jctr.20210901.12

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ACS Style

Songbo Zhao; Chao Wu; Jialu Li; Yafen Li; Gangli An, et al. Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma. J. Cancer Treat. Res. 2021, 9(1), 10-21. doi: 10.11648/j.jctr.20210901.12

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AMA Style

Songbo Zhao, Chao Wu, Jialu Li, Yafen Li, Gangli An, et al. Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma. J Cancer Treat Res. 2021;9(1):10-21. doi: 10.11648/j.jctr.20210901.12

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@article{10.11648/j.jctr.20210901.12,
  author = {Songbo Zhao and Chao Wu and Jialu Li and Yafen Li and Gangli An and Huimin Meng and Zixuan Li and Lin Yang},
  title = {Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma},
  journal = {Journal of Cancer Treatment and Research},
  volume = {9},
  number = {1},
  pages = {10-21},
  doi = {10.11648/j.jctr.20210901.12},
  url = {https://doi.org/10.11648/j.jctr.20210901.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jctr.20210901.12},
  abstract = {Multiple myeloma (MM) is a malignancy characterized by abnormal proliferation of clonal plasma cells, and it is the second most common hematologic malignancy in the world after non-Hodgkin lymphoma. In recent years, significant progress has been made in the clinical treatment of MM. In particular, certain novel drugs, such as bortezomib, lenalidomide, and carfilzomib, have greatly improved the survival rate of patients with MM. However, because of drug resistance, most MM patients eventually suffer a relapse and die of the disease. In this study, the chimeric antigen receptor-modified T cell (CAR-T cell) technology, which has achieved success in recent clinical trials for B-cell acute lymphoblastic leukemia (B-ALL), was used. In view of the high CD138 expression in MM cells and the presence of the CD138–/CD19+ phenotype in a small subset of MM cells, and based on preliminary findings of effective killing of MM cells by CD19-CAR-T cells in clinical studies, CD138- and CD19-directed CAR-T cells were constructed. Through in vitro experiments and the use of a mouse model, we proved that these two types of CAR-T cells possess strong biological activity in the specific killing of target cells, and that the concomitant use of these cells significantly enhances the killing effect in an MM mouse model.},
 year = {2021}
}

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TY  - JOUR
T1  - Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma
AU  - Songbo Zhao
AU  - Chao Wu
AU  - Jialu Li
AU  - Yafen Li
AU  - Gangli An
AU  - Huimin Meng
AU  - Zixuan Li
AU  - Lin Yang
Y1  - 2021/05/26
PY  - 2021
N1  - https://doi.org/10.11648/j.jctr.20210901.12
DO  - 10.11648/j.jctr.20210901.12
T2  - Journal of Cancer Treatment and Research
JF  - Journal of Cancer Treatment and Research
JO  - Journal of Cancer Treatment and Research
SP  - 10
EP  - 21
PB  - Science Publishing Group
SN  - 2376-7790
UR  - https://doi.org/10.11648/j.jctr.20210901.12
AB  - Multiple myeloma (MM) is a malignancy characterized by abnormal proliferation of clonal plasma cells, and it is the second most common hematologic malignancy in the world after non-Hodgkin lymphoma. In recent years, significant progress has been made in the clinical treatment of MM. In particular, certain novel drugs, such as bortezomib, lenalidomide, and carfilzomib, have greatly improved the survival rate of patients with MM. However, because of drug resistance, most MM patients eventually suffer a relapse and die of the disease. In this study, the chimeric antigen receptor-modified T cell (CAR-T cell) technology, which has achieved success in recent clinical trials for B-cell acute lymphoblastic leukemia (B-ALL), was used. In view of the high CD138 expression in MM cells and the presence of the CD138–/CD19+ phenotype in a small subset of MM cells, and based on preliminary findings of effective killing of MM cells by CD19-CAR-T cells in clinical studies, CD138- and CD19-directed CAR-T cells were constructed. Through in vitro experiments and the use of a mouse model, we proved that these two types of CAR-T cells possess strong biological activity in the specific killing of target cells, and that the concomitant use of these cells significantly enhances the killing effect in an MM mouse model.
VL  - 9
IS  - 1
ER  -

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Author Information

Songbo Zhao

The Cyrus Tang Hematology Center, Soochow University, Suzhou, PR China
Chao Wu

The Cyrus Tang Hematology Center, Soochow University, Suzhou, PR China
Jialu Li

The Cyrus Tang Hematology Center, Soochow University, Suzhou, PR China
Yafen Li

Persongen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, PR China
Gangli An

The Cyrus Tang Hematology Center, Soochow University, Suzhou, PR China
Huimin Meng

The Cyrus Tang Hematology Center, Soochow University, Suzhou, PR China
Zixuan Li

The Cyrus Tang Hematology Center, Soochow University, Suzhou, PR China
Lin Yang

The Cyrus Tang Hematology Center, Soochow University, Suzhou, PR China

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APA Style

Songbo Zhao, Chao Wu, Jialu Li, Yafen Li, Gangli An, et al. (2021). Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma. Journal of Cancer Treatment and Research, 9(1), 10-21. https://doi.org/10.11648/j.jctr.20210901.12

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ACS Style

Songbo Zhao; Chao Wu; Jialu Li; Yafen Li; Gangli An, et al. Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma. J. Cancer Treat. Res. 2021, 9(1), 10-21. doi: 10.11648/j.jctr.20210901.12

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AMA Style

Songbo Zhao, Chao Wu, Jialu Li, Yafen Li, Gangli An, et al. Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma. J Cancer Treat Res. 2021;9(1):10-21. doi: 10.11648/j.jctr.20210901.12

Copy | Download

@article{10.11648/j.jctr.20210901.12,
  author = {Songbo Zhao and Chao Wu and Jialu Li and Yafen Li and Gangli An and Huimin Meng and Zixuan Li and Lin Yang},
  title = {Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma},
  journal = {Journal of Cancer Treatment and Research},
  volume = {9},
  number = {1},
  pages = {10-21},
  doi = {10.11648/j.jctr.20210901.12},
  url = {https://doi.org/10.11648/j.jctr.20210901.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jctr.20210901.12},
  abstract = {Multiple myeloma (MM) is a malignancy characterized by abnormal proliferation of clonal plasma cells, and it is the second most common hematologic malignancy in the world after non-Hodgkin lymphoma. In recent years, significant progress has been made in the clinical treatment of MM. In particular, certain novel drugs, such as bortezomib, lenalidomide, and carfilzomib, have greatly improved the survival rate of patients with MM. However, because of drug resistance, most MM patients eventually suffer a relapse and die of the disease. In this study, the chimeric antigen receptor-modified T cell (CAR-T cell) technology, which has achieved success in recent clinical trials for B-cell acute lymphoblastic leukemia (B-ALL), was used. In view of the high CD138 expression in MM cells and the presence of the CD138–/CD19+ phenotype in a small subset of MM cells, and based on preliminary findings of effective killing of MM cells by CD19-CAR-T cells in clinical studies, CD138- and CD19-directed CAR-T cells were constructed. Through in vitro experiments and the use of a mouse model, we proved that these two types of CAR-T cells possess strong biological activity in the specific killing of target cells, and that the concomitant use of these cells significantly enhances the killing effect in an MM mouse model.},
 year = {2021}
}

Copy | Download

TY  - JOUR
T1  - Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma
AU  - Songbo Zhao
AU  - Chao Wu
AU  - Jialu Li
AU  - Yafen Li
AU  - Gangli An
AU  - Huimin Meng
AU  - Zixuan Li
AU  - Lin Yang
Y1  - 2021/05/26
PY  - 2021
N1  - https://doi.org/10.11648/j.jctr.20210901.12
DO  - 10.11648/j.jctr.20210901.12
T2  - Journal of Cancer Treatment and Research
JF  - Journal of Cancer Treatment and Research
JO  - Journal of Cancer Treatment and Research
SP  - 10
EP  - 21
PB  - Science Publishing Group
SN  - 2376-7790
UR  - https://doi.org/10.11648/j.jctr.20210901.12
AB  - Multiple myeloma (MM) is a malignancy characterized by abnormal proliferation of clonal plasma cells, and it is the second most common hematologic malignancy in the world after non-Hodgkin lymphoma. In recent years, significant progress has been made in the clinical treatment of MM. In particular, certain novel drugs, such as bortezomib, lenalidomide, and carfilzomib, have greatly improved the survival rate of patients with MM. However, because of drug resistance, most MM patients eventually suffer a relapse and die of the disease. In this study, the chimeric antigen receptor-modified T cell (CAR-T cell) technology, which has achieved success in recent clinical trials for B-cell acute lymphoblastic leukemia (B-ALL), was used. In view of the high CD138 expression in MM cells and the presence of the CD138–/CD19+ phenotype in a small subset of MM cells, and based on preliminary findings of effective killing of MM cells by CD19-CAR-T cells in clinical studies, CD138- and CD19-directed CAR-T cells were constructed. Through in vitro experiments and the use of a mouse model, we proved that these two types of CAR-T cells possess strong biological activity in the specific killing of target cells, and that the concomitant use of these cells significantly enhances the killing effect in an MM mouse model.
VL  - 9
IS  - 1
ER  -

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