Bispecific therapeutics: a state-of-the-art review on the combination of immune checkpoint ‎inhibition with costimulatory and non-checkpoint targeted therapy

Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer immunotherapy and have enhanced the survival of patients with malignant tumors. However, the overall efficacy of ICIs remains unsatisfactory and is faced with two major concerns of resistance development and occurrence of immune-related adverse events (irAEs). Bispecific antibodies (bsAbs) have emerged as promising strategies with unique mechanisms of action to achieve a better efficacy and safety than monoclonal antibodies (mAbs) or even their combination. BsAbs along with other bispecific platforms such as bispecific fusion proteins, nanobodies, and CAR-T cells may help to avoid development of resistance and reduce irAEs caused by on-target/off-tumor binding effects of mAbs.