Development of a unique anti-CD137 therapeutic antibody: Efficacy and safety profiles in mono and combination therapy.

e23079Background: Abstract: CD137 (4-1BB), a member of the TNFR super family, is expressed on several subsets of activated immune cells and acts as co-stimulatory receptor for T-cells to promote cellular proliferation, survival and cytokine production. Agonist antibodies against human CD137 in early clinical trials show strikingly different toxicology profiles, ranging from severe liver toxicity at low doses, to manageable adverse effects at modest doses. Whereas preclinical studies in mouse show intense liver T-cell infiltration and toxicity by surrogate agonist mAb. The preclinical efficacy and pharmacology of anti-CD137 were extensively tested and validated in various tumor models with intact immune system. Since none of the available anti-CD137 agonist antibodies display multiple species cross reactivity including rodent, the translational significance of these mAbs is limited concerning their efficacy and safety profile. Methods: Through our proprietary Dynamic Precision Library (DPL) technology, we ...