Bispecific

Bispecific refers to molecules engineered to recognize two distinct targets, typically two different antigens or two epitopes on the same antigen. In biopharmaceuticals, the term most often describes bispecific antibodies (bsAbs), which can be built in a variety of formats. Some are full-length IgG-like antibodies with two different binding sites; others use fragments or fusion constructs such as BiTEs (bispecific T-cell engagers), DARTs, or tandem single-chain variable fragments. Some bispecifics pair a targeting domain with a toxic payload or a signaling modulator.

By binding two targets, these agents can perform functions that single-target antibodies cannot. Common mechanisms include redirecting immune effector cells to diseased cells, simultaneously blocking two signaling pathways, or bringing two receptors into proximity to alter downstream signaling. This versatility makes bispecifics a focus in oncology, ophthalmology, and some autoimmune contexts.

Clinical examples illustrate the range of designs. Blinatumomab is a CD3 x CD19 bispecific antibody that engages T cells to kill B-cell leukemias. Amivantamab targets EGFR and MET and is approved for certain EGFR-mutated non-small cell lung cancers. Mosunetuzumab and epcoritamab are CD20 x CD3 bispecific antibodies used in B-cell lymphoma settings. Faricimab, a VEGF-A x angiopoietin-2 bispecific, is used for neovascular eye diseases such as age-related macular degeneration.

Production and development of bsAbs remain technically challenging due to complexity, stability, and immunogenicity considerations. Safety concerns include cytokine release syndrome and off-target toxicities. Ongoing research seeks to expand indications and refine formats to improve efficacy, safety, and patient convenience.