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Review

Antibody-Drug Conjugates: The New Frontier of Chemotherapy

by
Sara Ponziani
1,†,
Giulia Di Vittorio
2,†,
Giuseppina Pitari
1,
Anna Maria Cimini
1,
Matteo Ardini
1,
Roberta Gentile
2,
Stefano Iacobelli
2,
Gianluca Sala
2,3,
Emily Capone
3,
David J. Flavell
4,
Rodolfo Ippoliti
1 and
Francesco Giansanti
1,*
1
Department of Life, Health and Environmental Sciences, University of L’Aquila, I-67100 L’Aquila, Italy
2
MediaPharma SrL, I-66013 Chieti, Italy
3
Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, I-66100 Chieti, Italy
4
The Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, Southampton SO16 6YD, UK
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(15), 5510; https://doi.org/10.3390/ijms21155510
Submission received: 14 July 2020 / Revised: 29 July 2020 / Accepted: 30 July 2020 / Published: 31 July 2020
(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy)
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Abstract

In recent years, antibody-drug conjugates (ADCs) have become promising antitumor agents to be used as one of the tools in personalized cancer medicine. ADCs are comprised of a drug with cytotoxic activity cross-linked to a monoclonal antibody, targeting antigens expressed at higher levels on tumor cells than on normal cells. By providing a selective targeting mechanism for cytotoxic drugs, ADCs improve the therapeutic index in clinical practice. In this review, the chemistry of ADC linker conjugation together with strategies adopted to improve antibody tolerability (by reducing antigenicity) are examined, with particular attention to ADCs approved by the regulatory agencies (the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA)) for treating cancer patients. Recent developments in engineering Immunoglobulin (Ig) genes and antibody humanization have greatly reduced some of the problems of the first generation of ADCs, beset by problems, such as random coupling of the payload and immunogenicity of the antibody. ADC development and clinical use is a fast, evolving area, and will likely prove an important modality for the treatment of cancer in the near future.
Keywords: Mabs; Antibody-Drug Conjugate; cancer therapy; drug targeting; payload; cross-linking Mabs; Antibody-Drug Conjugate; cancer therapy; drug targeting; payload; cross-linking
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MDPI and ACS Style

Ponziani, S.; Di Vittorio, G.; Pitari, G.; Cimini, A.M.; Ardini, M.; Gentile, R.; Iacobelli, S.; Sala, G.; Capone, E.; Flavell, D.J.; et al. Antibody-Drug Conjugates: The New Frontier of Chemotherapy. Int. J. Mol. Sci. 2020, 21, 5510. https://doi.org/10.3390/ijms21155510

AMA Style

Ponziani S, Di Vittorio G, Pitari G, Cimini AM, Ardini M, Gentile R, Iacobelli S, Sala G, Capone E, Flavell DJ, et al. Antibody-Drug Conjugates: The New Frontier of Chemotherapy. International Journal of Molecular Sciences. 2020; 21(15):5510. https://doi.org/10.3390/ijms21155510

Chicago/Turabian Style

Ponziani, Sara, Giulia Di Vittorio, Giuseppina Pitari, Anna Maria Cimini, Matteo Ardini, Roberta Gentile, Stefano Iacobelli, Gianluca Sala, Emily Capone, David J. Flavell, and et al. 2020. "Antibody-Drug Conjugates: The New Frontier of Chemotherapy" International Journal of Molecular Sciences 21, no. 15: 5510. https://doi.org/10.3390/ijms21155510

APA Style

Ponziani, S., Di Vittorio, G., Pitari, G., Cimini, A. M., Ardini, M., Gentile, R., Iacobelli, S., Sala, G., Capone, E., Flavell, D. J., Ippoliti, R., & Giansanti, F. (2020). Antibody-Drug Conjugates: The New Frontier of Chemotherapy. International Journal of Molecular Sciences, 21(15), 5510. https://doi.org/10.3390/ijms21155510

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