Targeted cellular immunotherapy with bifunctional antibodies (bsAbs) has emerged as a
promising therapeutic approach for cancer over the last two decades. Progress in antibody engineering
has led to the generation of many different types of antibody-derived entities that display at least two
binding specificities. Most bsAbs consist of large IgG-like proteins with multiple antigen-binding regions
containing Fc parts or smaller entities without Fc. BsAbs have the potential to engage effector
cells of the immune system, thereby overcoming some of the immune response escape mechanisms of
tumor cells. Preclinical and clinical trials of various bsAb constructs have demonstrated impressive results in terms of
immune effector cell retargeting and induction of efficient anti-tumor responses. This review provides an overview of the
established bsAbs focusing on improvements in format and design as well as the mechanisms of action of the most promising
candidates and describes the results of the most recent clinical studies.
Keywords: Bispecific antibody, antibody engineering, cancer, immunotherapy, clinical trials, T cells, NK cells, cell death.
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