ANTIBODY-DRUG CONJUGATES AND BISPECIFIC ANTIBODIES: THE NEW CORNERSTONES OF TARGETED CANCER THERAPY

Ancelin Wilfy* and Mukesh M.

ADCs and BsAbs herald a new era for targeted cancer therapies with enhanced specificity, less systemic toxicity, and better clinical outcomes. ADCs are conjugates comprising monoclonal antibodies and potent cytotoxic drugs. They provide in vitro tumor cell death mediated by binding and cellular uptake of monoclonal antibody into the undesirable cells. BsAbs in contrast bind tumor-associated antigens at one end and immune effector cells at the other, essentially redirecting the immune system to kill tumor cells. Both modalities, however, present clinical advantages for the treatment of hematologic and solid malignancies with many of the variants already having gained regulatory approval, while many others are still at different stages of clinical development. Certainly, resistance, restricted antigen expression, and toxicities caused by cytokines are some of the challenges faced. However, recent advances in antibody engineering, linker, and payload design have rapidly eliminated these pitfalls. This review focuses on the structure, mechanism, clinical applications, current approvals, and potential advances to date in the field of ADCs and BsAbs that are set to transform cancer therapeutics for future precision medicine.