A comprehensive review of key factors affecting the efficacy of antibody drug conjugate

Abstract

Antibody Drug Conjugate (ADC) is an emerging technology to overcome the limitations of chemotherapy by selectively targeting the cancer cells. ADC binds with an antigen, specifically over expressed on the surface of cancer cells, results decrease in bystander effect and increase in therapeutic index. The potency of an ideal ADC is entirely depending on several physicochemical factors such as site of conjugation, molecular weight, linker length, Steric hinderance, half-life, conjugation method, binding energy and so on. Inspite of the fact that there is more than 100 of ADCs are in clinical trial only 14 ADCs are approved by FDA for clinical use. However, to design an ideal ADC is still challenging and there is much more to be done. Here in this review, we have discussed the key components along with their significant role or contribution towards the efficacy of an ADC. Moreover, we also explained about the recent advancement in the conjugation method. Additionally, we spotlit the mode of action of an ADC, recent challenges, and future perspective regarding ADC. The profound knowledge regarding key components and their properties will help in the synthesis or production of different engineered ADCs. Therefore, contributes to develop an ADC with low safety concern and high therapeutic index. We hope this review will improve the understanding and encourage the practicing of research in anticancer ADCs development.

Keywords: Antibody-drug conjugate; Bispecific antibodies; Conjugation method; Linker; Next generation ADC; Steric hinderance; Tumor Microenvironment.