Antibody-drug conjugates (ADCs) have emerged as a promising approach in cancer therapy, offering a 'magic bullet' strategy that combines the precision of monoclonal antibodies with the potency of cytotoxic drugs. The evolution of ADCs has seen significant advancements from first-generation Mylotarg, which was initially approved and later withdrawn due to stability and toxicity issues, to second- and third-generation ADCs that have optimized linker technology and improved stability and efficacy. To date, fifteen ADCs have been approved by regulatory agencies worldwide, with many more in various clinical trial phases, showcasing the rapid progression in this field.
Bispecific ADCs represent a cutting-edge advancement, leveraging bispecific antibodies that can target two distinct antigens or epitopes, enhancing the therapeutic index of ADCs by increasing selectivity and reducing off-tumor toxicity. These bispecific constructs have demonstrated the potential to overcome drug resistance, increase internalization rates, and improve the safety profile of ADCs. The mechanism of action of bispecific ADCs involves binding to multiple antigens, facilitating receptor clustering and internalization, and releasing cytotoxic payloads within tumor cells, leading to apoptosis.
This dual-targeting strategy can also induce a bystander effect, where the released payload affects neighboring tumor cells. Several bispecific ADCs are in clinical development, targeting a range of cancers with differe.
