Uncoupling Efficacy from Toxicity: A Case Study on MEDI5752
MEDI5752 also displayed a strong and dose-dependent anti-tumor activity, demonstrating the bispecific antibody’s efficacy. Additionally, a single dose of MEDI5752 led to increased survival compared to anti-PD-1 and/or anti-CTLA-4 mAbs treatments (Fig.2B).
These data demonstrate the efficacy of this new bispecific antibody MEDI5752 over conventional combination therapy, and suggest that its preferential localization to the tumor could reduce treatment-associated adverse effects.
Interestingly, two patients with advanced solid tumors positively responded to MEDI5752 treatment, thus supporting the translational relevance of these findings. Taken together, these findings show that MEDI5752 represents a novel immunotherapy that provides modulated CTLA-4 inhibition while suppressing the PD-1 pathway, thereby uncoupling CTLA-4-dependent peripheral toxicity from anti-tumor efficacy.3
Of note, the double humanized mouse preclinical model used in this study was generated by genOway, designer and provider of multiple preclinical models in immuno-oncology. This specific model enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint PD-1 and/or CTLA-4 in fully immunocompetent mice. Importantly, it has been co-validated by partners of the precompetitive consortium of company leaders in immuno-oncology and immunotherapy.