Antibody–drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes

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  • Meghdad Abdollahpour‐Alitappeh
    Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL) Baqiyatallah University of Medical Sciences Tehran Iran
  • Majid Lotfinia
    Gastroenterology and Liver Diseases Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran Iran
  • Tohid Gharibi
    Immunology Research Center Tabriz University of Medical Sciences Tabriz Iran
  • Jalal Mardaneh
    Department of Microbiology School of Medicine, Gonabad University of Medical Sciences Gonabad Iran
  • Behrouz Farhadihosseinabadi
    Department of Pharmacology School of Medicine, Shahid Beheshti University of Medical Sciences Tehran Iran
  • Pegah Larki
    Gastroenterology and Liver Diseases Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran Iran
  • Babak Faghfourian
    Department of Cardiology School of Medicine, Hamedan University of Medical Sciences Hamedan Iran
  • Koushan Sineh Sepehr
    Laboratory Sciences Research Center Golestan University of Medical Sciences Gorgan Iran
  • Kazem Abbaszadeh‐Goudarzi
    Cellular and Molecular Research Center Sabzevar University of Medical Sciences Sabzevar Iran
  • Ghasem Abbaszadeh‐Goudarzi
    Department of Medical Biotechnology School of Medicine, Shahroud University of Medical Sciences Shahroud Iran
  • Behrooz Johari
    Department of Medical Biotechnology and Nanotechnology School of Medicine, Zanjan University of Medical Science Zanjan Iran
  • Mohammad Reza Zali
    Gastroenterology and Liver Diseases Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran Iran
  • Nader Bagheri
    Cellular and Molecular Research Center Basic Health Sciences Institute, Shahrekord University of Medical Sciences Shahrekord Iran

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<jats:title>Abstract</jats:title><jats:p>Targeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody–drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more‐stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.</jats:p>

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