Bispecific antibodies have been shown to have several distinct advantages over monoclonal antibodies. However, testing their effectiveness and safety in vivo has proven to be a specific challenge for this promising therapeutic class. The researchers at JAX have developed a human stem cell (HSC) humanized mouse model for testing both efficacy and quantifying cytokine release in response to bispecific antibody treatment.
In a recent poster, Yao and colleagues from JAX presented their work, which evaluated an EGFR bispecific T cell engager (), using an EGFR-positive MDA-MD-231 orthotopic breast cancer model in a CD34+ HSC NSG™ mouse model.
In terms of efficacy, the authors observed that there was complete tumor regression in 2 weeks post treatment. Furthermore, at four weeks post-treatment, tumors at approximately 400 mm3 were inhibited. To assess immunotoxicity, 16 hours following the first two doses of treatment, the authors observed elevated levels of human cytokines IFN-g, IL-6, and IL-10. However, following continuous dosing, these levels returned to baseline.