Development of an EGFR-targeted CAR T-cell immunotherapy in head and neck cancer

Introduction Immunotherapy is an effective, innovative option for the treatment squamous cell carcinomas of the head and neck (HNSCC). EGFR (epidermal growth factor receptor) targeting antbodies are an established therapy. Next to checkpoint inhibitors, immunotherapy with CAR (chimeric antigen receptor) T-cells is an emerging option. According to this, we established an EGFR-targeting immunotherapy for HNSCC in vitro.

Methods The EGFR-expression of 33 HNSCC cell lines was determined using flow cytometry. CARs containing either Cetuximab-based or a Nimotuximab-based elements were cloned and lentivirally transduced to T-cells. Cytoxity of CAR T cells was determined after co-cultivation with tumor cells and tumor cells survival measured by MTS (CellTiter proliferation assay).

Results EGFR is overexpressed in 78 % of the cell lines and therefore a good target for immunotherapy. To improve the proportion of CAR positive T cells for a more effective therapy, we raised the viral titer by concentrating the viral supernatant. The proportion of CAR positive T cells was increased 3,5-fold. Cetuximab-based CAR effectively lysed the tumor cells, while the Nimotuzumab-based CAR did not.

Conclusion With this study we laid the foundation for a new type of immunotherapy for HNSCC using a therapeutically effective EGFR-directed CAR for adoptive T-cell transfer.

Poster-PDF A-1737.PDF

Publication History

Article published online:
10 June 2020