This study investigates the efficacy and safety of INA03, a novel antibody–drug conjugate (ADC) targeting CD71 (transferrin receptor 1), in the treatment of acute leukemia. The research evaluates INA03's binding affinity, internalization, cytotoxic effects on leukemic cells, and its safety profile in preclinical models.
INA03 demonstrated high specificity and affinity for human CD71, effectively inducing cell death in CD71-expressing leukemic cells. In vivo, INA03 treatment significantly reduced tumor burden and increased survival in acute leukemia mouse models. Importantly, administration of INA03 in the double humanized hCD71/hTf mice did not result in significant toxicities, even at high doses, indicating a favorable safety profile.
The study utilized a double humanized mouse model developed in collaboration with genOway. This model expresses human CD71 (hCD71) and human transferrin (hTf), allowing for the assessment of INA03's pharmacokinetics, pharmacodynamics, and potential toxicities in a system that closely mimics human physiology. The humanization was achieved through targeted replacement of the murine Tfrc and Tf genes with their human counterparts, ensuring physiological expression patterns and functional interactions.
Acute leukemia, Antibody–drug conjugate, Targeted therapy, Hematologic malignancies, Preclinical evaluation
Double humanized mouse model, Human gene replacement, Physiological expression, Pharmacokinetics assessment, Toxicity 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
