Leveraging HER2-targeted biparatopic antibodies in solid tumors

Abstract

Biparatopic antibodies (bpAbs), which target non-overlapping epitopes on the same antigen, offer unique mechanisms of action and therapeutic applications that surpass those of conventional monospecific antibodies. These distinctive properties have positioned bpAbs as effective therapeutic agents in the treatment of cancer and infectious diseases, especially in cases where current treatments face limitations. Among these, HER2-targeted bpAbs have shown significant improvements in survival outcomes for patients with solid tumors that depend on HER2 signaling. However, a comprehensive understanding of their clinical impact, mechanisms of action, and limitations in therapeutic use remains lacking. Here, we review and contrast the clinical performance of the well-established HER2-targeted bpAbs in current use, with a focus on their mechanisms of action, associated limitations, and potential combination strategies. We also highlight emerging investigational bpAbs-based agents that have shown promise in the treatment of HER2-positive solid cancers. These advancements may lead to enhanced therapeutic options and potentially broaden the scope of bpAbs in cancer therapy.