Title:ADCs, as Novel Revolutionary Weapons for Providing a Step Forward in Targeted Therapy of Malignancies
Volume: 17
Issue: 1
Author(s): Nooshafarin Amani*, Farid Abedin Dorkoosh and Hamid Mobedi
Affiliation:
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran,Iran
Keywords:
Immuno conjugate, selective targeting strategy, site-specific conjugation, antibody, drug delivery, hematological
and solid tumor.
Abstract: Antibody drug conjugates (ADCs), as potent pharmaceutical trojan horses for cancer treatment,
provide superior efficacy and specific targeting along with low risk of adverse reactions compared
to traditional chemotherapeutics. In fact, the development of these agents combines the selective
targeting capability of monoclonal antibody (mAb) with high cytotoxicity of chemotherapeutics for
controlling the neoplastic mass growth. Different ADCs (more than 60 ADCs) in preclinical and clinical
trials were introduced in this novel pharmaceutical field. Various design-based factors must be taken
into account for improving the functionality of ADC technology, including selection of appropriate
target antigen and high binding affinity of fragment (miniaturized ADCs) or full mAbs (preferentially
use of humanized or fully human antibodies compared to murine and chimeric ones), use of bispecific
antibodies for dual targeting effect, linker engineering and conjugation method efficacy to obtain more
controlled drug to antibody ratio (DAR). Challenging issues affecting therapeutic efficacy and safety of
ADCs, including bystander effect, on- and off-target toxicities, multi drug resistance (MDR) are also
addressed. 4 FDA-approved ADCs in the market, including ADCETRIS ®, MYLOTARG®, BESPONSA
®, KADCYLA®. The goal of the current review is to evaluate the key parameters affecting
ADCs development.
