This study presents the development and preclinical evaluation of MEDI5752, a monovalent bispecific antibody targeting PD-1 and CTLA-4. MEDI5752 is designed to preferentially inhibit CTLA-4 on PD-1+ activated T cells, enhancing antitumor immunity while potentially reducing immune-related adverse events associated with combination checkpoint blockade. The antibody demonstrated preferential binding to PD-1+ T cells, induced rapid internalization and degradation of PD-1, and showed superior antitumor activity compared to the combination of anti-PD-1 and anti-CTLA-4 monoclonal antibodies in humanized mouse models.
MEDI5752 preferentially targets PD-1+ T cells, enhances CTLA-4 blockade, induces PD-1 degradation, and exhibits superior antitumor efficacy with potentially reduced toxicity compared to combination therapy.
Human PD-1 and CTLA-4 double Knockin mouse model expressing human PD-1 and CTLA-4 proteins, used to evaluate the in vivo efficacy and pharmacodynamics of MEDI5752.
Cancer immunotherapy, Immune checkpoint blockade, Bispecific antibody, PD-1, CTLA-4
Humanized Knockin model, PD-1 and CTLA-4 gene replacement, Bispecific antibody evaluation
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
