Abstract
The switchable chimeric antigen receptors (CARs) have shown many advantages in CAR T-cell therapy. However, human primary T-cells are required to evaluate antigen-specific adaptors by IFN-γ assay or FACS analysis, which limits the throughput of adaptor screening. A sensitive and robust CD16-CAR Jurkat NFAT-eGFP reporter system has been developed to assess the therapeutic efficacy of antibody-targeted CAR-T-cell by effectively evaluating the T-cell activation by various tumor cells and the impact of immune checkpoint inhibitor antibodies. This reporter system facilitates the screening of targeted antibodies in a high throughput manner for the development of improved T-cell immunotherapy.
Keywords:
CD16-CAR; PD-L1; cetuximab; immunotherapy.
MeSH terms
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A549 Cells
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Antibodies, Monoclonal, Humanized / pharmacology*
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Antineoplastic Agents, Immunological / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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B7-H1 Antigen / antagonists & inhibitors*
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B7-H1 Antigen / immunology
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B7-H1 Antigen / metabolism
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Cetuximab / pharmacology*
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Drug Screening Assays, Antitumor
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / immunology
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ErbB Receptors / metabolism
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GPI-Linked Proteins / genetics
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GPI-Linked Proteins / immunology
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GPI-Linked Proteins / metabolism
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Genes, Reporter
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Green Fluorescent Proteins / biosynthesis
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Green Fluorescent Proteins / genetics
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HCT116 Cells
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High-Throughput Screening Assays
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Humans
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Immune Checkpoint Inhibitors / pharmacology*
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Immunotherapy, Adoptive*
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Jurkat Cells
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NFATC Transcription Factors / genetics
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Neoplasms / genetics
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Neoplasms / immunology
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Neoplasms / metabolism
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Neoplasms / therapy*
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Receptors, Chimeric Antigen / genetics
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Receptors, Chimeric Antigen / immunology*
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Receptors, Chimeric Antigen / metabolism
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Receptors, IgG / genetics
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Receptors, IgG / immunology*
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Receptors, IgG / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / transplantation*
Substances
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents, Immunological
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B7-H1 Antigen
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CD274 protein, human
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FCGR3B protein, human
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GPI-Linked Proteins
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Immune Checkpoint Inhibitors
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NFATC Transcription Factors
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Receptors, Chimeric Antigen
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Receptors, IgG
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enhanced green fluorescent protein
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Green Fluorescent Proteins
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atezolizumab
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EGFR protein, human
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ErbB Receptors
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Cetuximab