Antibody-Drug Conjugates as a Targeted Therapeutic Approach Across Entities in Oncology
Florian Lordick1, Maximilian Merz, Eva Büch
1Department of Oncology, Gastroenterology, Hepatology, Pulmonology, University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany, Leipzig, Germany; Department of Hematology, Cell therapy und Hemostaseology, University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany, Leipzig, Germany; Rudolf Boehm Institute of Pharmacology and Toxicology, Independent Department of Clinical Pharmacology, Medical Faculty, University of Leipzig, Comprehensive Cancer Center Central Germany, Leipzig, Germany.
Background:
Cancer is no longer treated on the basis of its histological lineage alone; more and more drugs are being developed that are directed toward specific molecular and immunological features. Monoclonal antibodies are one type of selectively acting therapeutic agent. As part of this development, antibody-drug conjugates ("ADCs") have been approved in recent years for the treatment of hematologic and solid malignancies.
Methods:
This review is based on pertinent articles retrieved by a selective search in PubMed, as well as on papers presented at international congresses of specialist societies such as the European Society for Medical Oncology, the American Society of Clinical Oncology, and the American Association for Cancer Research, and information published on the websites of the European Medicines Agency, the Food and Drug Administration, and the German Joint Federal Committee.
Results:
The efficacy of the nine ADCs currently approved in the European Union (as of 12/2022) is derived from technical improvements in the conjugation process, the introduction of novel linkers for the covalent binding of cytotoxic agents to the Fc portion of the antibody, and the development of new, potent cytotoxic agents. Compared to conventional cancer therapies, the approved ADCs improve treatment outcomes with respect to tumor remission, time to tumor progression and, in some cases, overall survival by specifically channeling cytotoxic agents into the malignant target cells and thereby limiting, at least to some extent, the exposure of healthy tissue to adverse effects. Various potential side effects still require attention, including venous occlusive disease, pneumonitis, ocular keratopathy, and skin rash. The development of effective ADCs requires the identification of tumor-selective targets to which ADCs can bind.
Conclusion:
ADCs are a novel category of drugs for the treatment of cancer. Their approval is mainly, but not exclusively, based on the favorable findings of randomized, controlled phase III trials. ADCs are already helping to improve the outcomes of treatment for cancer.
Insights
Antibody-drug conjugates (ADCs) represent a novel class of cancer therapeutics. These targeted treatments improve outcomes by delivering cytotoxic agents specifically to cancer cells, enhancing efficacy and reducing side effects.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Cancer treatment is evolving beyond histology to target specific molecular and immunological features.
- Monoclonal antibodies are a key type of targeted therapeutic agent.
- Antibody-drug conjugates (ADCs) are increasingly approved for hematologic and solid malignancies.
Approach:
- This review synthesizes information from PubMed, major oncology congresses (ESMO, ASCO, AACR), and regulatory agency websites (EMA, FDA).
- The methodology involved a selective literature search and review of regulatory documentation.
Key Points:
- Nine ADCs approved in the EU (as of 12/2022) demonstrate efficacy due to improved conjugation, novel linkers, and potent cytotoxic agents.
- ADCs enhance tumor remission, delay progression, and improve survival by selectively targeting cancer cells.
- Potential side effects include pneumonitis, ocular keratopathy, and skin rash, necessitating careful monitoring.
Conclusions:
- ADCs are a significant advancement in cancer therapy, offering improved treatment outcomes.
- Approval of ADCs is largely supported by robust phase III clinical trial data.
- The development of ADCs relies on identifying specific tumor-selective targets for optimal efficacy.
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