Fine-Tuning T-Cell–Targeting Therapies Through Affinity Engineering & Dosing Strategy
- This presentation will discuss optimisation strategies for distinct T-cell–targeting modalities, focusing on (i) CD3 affinity modulation in T-cell engagers to improve the benefit–risk profile and (ii) adaptation of dosing frequency for T-cell costimulatory bispecific antibodies to enhance T-cell fitness and durability of antitumour immune responses in the clinic
- For CD3 affinity tuning, comparative in vitro and in vivo studies of two B7-H4– targeting CD3 bispecific antibodies demonstrated that lowering CD3 affinity resulted in reduced potency of tumour cell killing and cytokine secretion. The reduced potency was associated with better tolerability in cynomolgus monkeys
- For conditional T-cell co-stimulation, clinical data with acasunlimab (DuoBody- PD-L1×4-1BB) in combination with pembrolizumab show that a less frequent dosing paradigm results in intermittent target engagement, allowing for periods of T-cell rest and leading to improved magnitude and quality of anti-tumour immune responses