As we mentioned above, to bring about the most desirable effects, we must ensure the three components of ADC are well-chosen. In addition, the selection of clinically relevant targets and the position and number of linkages have also been the key determinants of ADC efficacy. So these are exactly what researchers are endeavored to do now.
Despite the fact that initially only two ADCs--brentuximab vedotin and trastuzumab emtansine (T-DM1)--have been approved by FDA to enter the market, considerable progress has been achieved in the past few decades, like higher levels of cytotoxic drug conjugation, lower levels of naked antibodies and more-stable linkers between the drug and the antibody. By learning lessons from failures, stresses are now laid on the following aspects:
Also, the selection and engineering of antibodies for site-specific drug conjugation, accompanied by the quest for new conjugation chemistries and mechanisms of action, are among top priorities in ADC research as they will contribute to increased stability and higher homogeneity.