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Updated: Jun 5, 2025
Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
Published on: June 13, 2019
Construction and characterization of a novel secreted MsC-CAR-T cell in solid tumors
Yuan Mao1, Yufeng Chen2, Xiaohui Yang3
1Department of Geriatric Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China; National Health Commission Key Laboratory of Antibody Techniques, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing, China.
Abstract:
The CD47-SIRPα signaling has been acknowledged as a significant immune checkpoint and CD47 blocking has been proved as a potential therapeutic strategy for the treatment of solid tumor. However, the potential application of CAR-T cells secreted antibody fragment simultaneously in solid tumor is rarely explored. In this study, we searched bioinformatic databases and investigated the characteristics of CD47 in solid tumors. Then we consulted bioinformatic databases to design, optimize and construct a novel MsC-CAR which could target MAGE-A1 and self-secrete CD47-scFv. The engineering T cells containing MsC-CAR were transfected, verified and characterized. The tumor-inhibitory role of MsC-CART cells was further determined in vitro and in vivo. The results showed that MsC-CARs were successfully constructed and MsC1-CARs demonstrated the preferable features of recognizing MAGE-A1 and secreting CD47-scFv. Engineering T cells transfecting with MsC1-CAR (MsC1-CART cells) exerted the prominent tumor-inhibitory effectiveness, both in different cancer cell lines and LUAD xenograft tumors. The present data highlighted that MsC1-CART cells elaborately combined the adoptive cellular immunotherapy and immune checkpoint inhibitor therapy, may represent a new direction for the treatment of MAGE-A1 positive solid tumors.
Insights
This study introduces novel engineered T cells (MsC1-CART) that target MAGE-A1 and secrete CD47-blocking antibodies. These cells show significant potential for treating MAGE-A1 positive solid tumors by combining immunotherapy and immune checkpoint blockade.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- CD47-SIRPα signaling acts as a crucial immune checkpoint in solid tumors.
- CD47 blockade is a promising therapeutic strategy for solid tumors.
- The combined use of CAR-T cells and antibody fragment secretion for solid tumors is underexplored.
Purpose of the Study:
- To investigate CD47 characteristics in solid tumors using bioinformatic databases.
- To design, optimize, and construct a novel MsC-CAR targeting MAGE-A1 and secreting CD47-scFv.
- To evaluate the tumor-inhibitory efficacy of engineered T cells (MsC1-CART) in vitro and in vivo.
Main Methods:
- Bioinformatic database searches for CD47 characteristics in solid tumors.
- Design and construction of a novel MAGE-A1 targeting CAR with self-secreting CD47-scFv (MsC-CAR).
- Transfection, verification, and characterization of engineered T cells (MsC-CART) and evaluation of their anti-tumor activity.
Main Results:
- Successful construction of MsC-CARs, with MsC1-CARs showing effective MAGE-A1 recognition and CD47-scFv secretion.
- MsC1-CART cells demonstrated significant tumor-inhibitory effectiveness against various cancer cell lines and in LUAD xenograft models.
- The engineered MsC1-CART cells effectively combine adoptive cellular immunotherapy with immune checkpoint inhibitor therapy.
Conclusions:
- MsC1-CART cells represent a novel therapeutic approach for MAGE-A1 positive solid tumors.
- This strategy integrates CAR-T cell therapy with immune checkpoint inhibition for enhanced anti-tumor activity.
- MsC1-CART cells offer a promising new direction for treating MAGE-A1 positive solid tumors.
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