Multispecific antibodies and their uses

Abstract

T cell engagers that target both CD3 and 4-1BB are described, in which both targeting portions have balanced activities to ensure efficacy and safety. For example, the anti-CD3 portion can have T cell activation activity in the range of 0.5 to 10 nM, and the anti-4-1BB portion can have 4-1BB signaling activation activity in the range of 0.05 to 1 nM. Enhanced anti-CD3 antibodies are also disclosed, which showed improved in vitro and in vivo stability while maintaining preferential affinity. These novel anti-CD3 sequences can be used alone or in T cell engagers, demonstrating great potential for clinical applications.