Advances in structural design of T cell-dependent bispecific antibodies
With the development of antibody engineering,a diverse range of structures for T cell-dependent bispecific antibodies targeting CD3 have been devised to meet the needs of various clinical therapies.T cell-dependent bispecific antibodies can be categorized into IgG-like and non-IgG-like formats based on the presence or absence of an Fc domain.The most common difficulty in manufacturing bispecific antibodies is the mispairing between light and heavy chains.To overcome this challenge,several techniques,such as knob-into-hole and CrossMab technologies,have been implemented for structural design.Given that the mechanism of action of T cell-dependent bispecific antibodies is to redirect T cells to tumor cells to induce a killing effect,abolishment of Fc domain effector function,the affinity design of the target,and the distance design of immune synapse formation are all focal points in the structural design of T cell-dependent bispecific antibodies.This review aims to provide an overview of recent advances in the structural design of T cell-dependent bispecific antibodies.
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