The epidermal growth factor receptor (EGFR) is selectively expressed on the surface of numerous tumours, it has therefore become one of the central targets for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR where it inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer. However, only 15-20% patients benefit from this drug underlying the necessity to find new strategies to improve cetuximab efficiency. We aim to develop a reliable preclinical mouse model in which to study the immune mechanisms that contribute to tumour rejection and to evaluate the efficacy of EGFR-targeted antibodies in combination with other therapeutic drugs.

We selected an anti-mouse EGFR mAb, 7A7, which has been reported to exhibit similar properties to its human counterpart. However, in our hands, 7A7 failed to specifically recognize mouse EGFR and therefore cannot be used as the mouse equivalent of cetuximab use in humans. We decided to develop a mouse model that would allow us to use cetuximab. To do this we developed a humanized mouse model in which human peripheral blood mononuclear cell (PBMC), or cord-blood stem cells (SCs), were transferred into NSG.A2 mice. We found human immune cells consistently reconstituted in both PBMC-NSG.A2 and SC-NSG.A2 mice. Next, we challenged the mice with KJD cells, a human SCC cell line that only expresses EGFR at very low levels, and found that KJD SCC tumor cells could successfully establish and grow in mice recipient of MHC-mismatched PBMC or SC. In the next step, we aim to analyse the treatment efficacy of cetuximab and cetuximab in combination with other therapeutic drugs, and specifically to study immune mechanisms underlying tumour regression in response to therapy.