multispecific

Multispecific is a term used in biology and medicine to describe molecules that can engage two or more distinct targets or antigens. In therapeutic contexts, multispecific agents are designed to combine activities against multiple biological pathways or cell types. The term encompasses bispecific (two targets), trispecific (three targets), and higher-order multispecific constructs.

The most developed class are multispecific antibodies, engineered proteins that incorporate binding sites for two or more antigens. A common subtype is the bispecific T-cell engager (BiTE), which binds CD3 on T cells and a tumor-associated antigen to recruit T cells to cancer cells. Other formats include bispecific antibodies that simultaneously block two receptors or that recruit immune cells through an Fc region or other adaptor.

Other multispecific formats include multispecific molecules that bring together enzymes and substrates, or receptor-agonist/antagonist combinations, and non-antibody constructs such as scFv fragments assembled into single chains, Fc-fusions, or adaptor proteins that recruit endogenous effector functions.

Advantages include enhanced targeting, potential to overcome resistance by hitting multiple pathways, and the ability to recruit immune cells. Challenges include complex manufacturing, stability, pharmacokinetics, and safety concerns such as cytokine release syndrome and off-target activity.

As of the 2020s, several multispecific antibodies have been approved, including blinatumomab (CD3/CD19) for certain leukemias, and amivantamab (EGFR/MET) for NSCLC. A broad pipeline targets oncology, autoimmune diseases, and infectious diseases, reflecting ongoing interest in multispecific strategies.