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

Area of Science:

• Immunology
• Cellular Therapy
• Biotechnology

Background:

• Switchable chimeric antigen receptors (CARs) offer advantages in CAR T-cell therapy.
• Current methods for evaluating antigen-specific adaptors require human primary T-cells, limiting screening throughput.
• Assays like IFN-γ and FACS analysis are time-consuming and not high-throughput.

Purpose of the Study:

• To develop a sensitive and robust reporter system for high-throughput screening of antibody adaptors in CAR T-cell therapy.
• To assess the therapeutic efficacy of antibody-targeted CAR T-cells.
• To evaluate T-cell activation by tumor cells and the impact of immune checkpoint inhibitors.

Main Methods:

• Development of a CD16-CAR Jurkat NFAT-eGFP reporter system.
• Utilizing the reporter system to assess T-cell activation in response to various tumor cells.
• Evaluating the impact of immune checkpoint inhibitor antibodies on T-cell activation.

Main Results:

• The CD16-CAR Jurkat NFAT-eGFP reporter system effectively evaluates T-cell activation.
• The system demonstrates sensitivity and robustness for assessing CAR T-cell therapeutic efficacy.
• Facilitates high-throughput screening of targeted antibodies.

Conclusions:

• The developed reporter system significantly enhances the screening process for CAR T-cell immunotherapy components.
• This system overcomes the throughput limitations associated with primary T-cell assays.
• It is a valuable tool for developing improved T-cell immunotherapies.