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A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
MST1R as a potential new target antigen of chimeric antigen receptor T cells to treat solid tumors
Wen An1, Ju-Seop Kang1, Sukjoong Oh2
1Department of Pharmacology & Clinical Pharmacology Lab, Hanyang University, Seoul 04763, Korea.
Abstract:
Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CAR-T cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF-β, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF-β, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF-β, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF-β. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.
Insights
Researchers identified MST1R as a potential new target antigen for chimeric antigen receptor T cell (CAR-T) therapy in solid tumors like breast, lung, and bladder cancers. This discovery could advance CAR-T immunotherapy for these challenging diseases.
Area of Science:
- Oncology
- Immunotherapy
- Bioinformatics
Background:
- Chimeric antigen receptor T cell (CAR-T) therapy shows promise for hematological malignancies but faces challenges in solid tumors.
- Identifying suitable tumor-associated antigens (TAAs) is crucial for effective CAR-T therapy in solid tumors.
Purpose of the Study:
- To identify common TAAs for CAR-T cell immunotherapy in solid tumors using a bioinformatics approach.
- To evaluate the potential of identified TAAs as therapeutic targets and progression indicators.
Main Methods:
- Utilized GEO and TCGA databases to identify differentially expressed genes (DEGs) as potential TAAs.
- Analyzed gene expression in normal tissues using MERAV to select ideal target genes.
- Investigated tumor microenvironment factors and their correlation with potential TAAs.
Main Results:
- Identified seven common DEGs: HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4.
- MST1R showed potential as a target antigen across breast cancer, lung adenocarcinoma, and bladder cancer.
- MST1R expression correlated positively with immunosuppressive factors like TGF-β, CTLA-4, and IFN-γ in certain cancers.
Conclusions:
- MST1R is a promising novel target antigen for CAR-T cell therapy in breast, lung, and bladder cancers.
- MST1R may serve as a progression indicator for bladder cancer.
- Further research is warranted to validate MST1R as a therapeutic target in solid tumors.
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