Antibody–Drug Conjugates—Evolution and Perspectives

• Published in: International journal of molecular sciences Vol. 25; no. 13; p. 6969
• Main Authors: Chis, Adriana Aurelia, Dobrea, Carmen Maximiliana, Arseniu, Anca Maria, Frum, Adina, Rus, Luca-Liviu, Cormos, Gabriela, Georgescu, Cecilia, Morgovan, Claudiu, Butuca, Anca, Gligor, Felicia Gabriela, Vonica-Tincu, Andreea Loredana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2024
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - therapeutic use; Antigens; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Cancer therapies; Chemotherapy; Clinical trials; Cytotoxicity; Drugs; FDA approval; Hematology; Humans; Immunoconjugates - chemistry; Immunoconjugates - therapeutic use; Immunotherapy; Laboratory animals; Leukemia; Lymphoma; Monoclonal antibodies; Neoplasms - drug therapy; Polypeptides; Toxicity; Tumors; linker; targeted therapy; antibody–drug conjugates; safety; cancer; clinical trials; monoclonal antibody; cytotoxic payload; efficacy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25136969

Antineoplastic therapy is one of the main research themes of this century. Modern approaches have been implemented to target and heighten the effect of cytostatic drugs on tumors and diminish their general/unspecific toxicity. In this context, antibody–drug conjugates (ADCs) represent a promising and successful strategy. The aim of this review was to assess different aspects regarding ADCs. They were presented from a chemical and a pharmacological perspective and aspects like structure, conjugation and development particularities alongside effects, clinical trials, safety issues and perspectives and challenges for future use of these drugs were discussed. Representative examples include but are not limited to the following main structural components of ADCs: monoclonal antibodies (trastuzumab, brentuximab), linkers (pH-sensitive, reduction-sensitive, peptide-based, phosphate-based, and others), and payloads (doxorubicin, emtansine, ravtansine, calicheamicin). Regarding pharmacotherapy success, the high effectiveness expectation associated with ADC treatment is supported by the large number of ongoing clinical trials. Major aspects such as development strategies are first discussed, advantages and disadvantages, safety and efficacy, offering a retrospective insight on the subject. The second part of the review is prospective, focusing on various plans to overcome the previously identified difficulties.