Antibody-drug conjugates for lymphoma patients: preclinical and clinical evidences
Marilia Barreca1, Noémie Lang2, Chiara Tarantelli3
1Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90123 Palermo, Italy.
Abstract:
Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper it provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed.
Insights
Antibody-drug conjugates (ADCs) offer targeted cancer therapy by linking potent drugs to antibodies. This revolutionary approach enhances efficacy and reduces toxicity for malignancies, including lymphoma.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in cancer treatment, offering targeted delivery of cytotoxic agents.
- ADCs combine monoclonal antibodies specific to tumor antigens with potent anti-cancer drugs via a linker, minimizing systemic toxicity.
- The targeted nature of ADCs allows for direct delivery of payloads to cancer cells, sparing healthy tissues.
Purpose of the Study:
- To provide a comprehensive overview of approved and emerging antibody-drug conjugates (ADCs) for lymphoma treatment.
- To discuss the fundamental components, mechanisms of action, and clinical development progress of ADCs in lymphoma therapy.
Main Methods:
- Review of approved ADCs by regulatory bodies like the FDA and EMA.
- Analysis of preclinical and clinical investigation data for ADCs in lymphoma.
- Discussion of ADC design principles, including antibody selection, payload, and linker technology.
Main Results:
- Several ADCs have received regulatory approval for various malignancies, including lymphoma.
- Over 100 ADCs are currently undergoing preclinical and clinical evaluation globally.
- ADCs demonstrate promising efficacy and improved safety profiles in clinical trials for lymphoma.
Conclusions:
- ADCs are a revolutionary therapeutic modality for malignancies, particularly effective in lymphoma treatment.
- Ongoing research and development are expanding the landscape of ADCs, offering new hope for patients.
- The targeted delivery mechanism of ADCs significantly improves therapeutic outcomes while reducing side effects.
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