The Targeting Effect of Cetuximab Combined with PD-L1 Blockade against EGFR-Expressing Tumors in a Tailored CD16-CAR T-Cell Reporter System

Cancer Invest. 2021 Apr;39(4):285-296. doi: 10.1080/07357907.2021.1894570. Epub 2021 Mar 11.

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

  • A549 Cells
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • Cetuximab / pharmacology*
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • GPI-Linked Proteins / metabolism
  • Genes, Reporter
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • HCT116 Cells
  • High-Throughput Screening Assays
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immunotherapy, Adoptive*
  • Jurkat Cells
  • NFATC Transcription Factors / genetics
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / immunology*
  • Receptors, Chimeric Antigen / metabolism
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology*
  • Receptors, IgG / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Immune Checkpoint Inhibitors
  • NFATC Transcription Factors
  • Receptors, Chimeric Antigen
  • Receptors, IgG
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • atezolizumab
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab