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Curr Drug Deliv. 2019 Nov 21. doi: 10.2174/1567201816666191121145109. [Epub ahead of print]

ADCs, as novel revolutionary weapons for providing a step forward in targeted therapy of malignancies.

Author information

1
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
2
Medical Biomaterial Research Center (MBRC), Tehran University of Medical Sciences, Tehran, Iran.
3
Novel Drug Delivery Systems (NDDS) Department, Iran Polymer and Petrochemical Institute, Tehran, Iran.

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 combine the selective targeting capability of monoclonal antibody (mAb) with high cytotoxicity of chemotherapeutics for controling 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 (prefentially 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®. Goal of current review is to evaluate the key parameters affecting ADCs development.

KEYWORDS:

Antibody; Drug delivery; Hematological and solid tumor; Immuno conjugate; Selective targeting strategy; Site-specific conjugation

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