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Adecatumumab: an anti-EpCAM monoclonal antibody, from the bench to the bedside
Jean-Emmanuel Kurtz1, Patrick Dufour
1Département d'Hématologie et d'Oncologie, Hôpitaux Universitaires de Strasbourg, Avenue Molière, 67200 Strasbourg, France.
Importance Of The Field:
In developing new anticancer drugs, the identification of relevant targets is a key issue of growing importance. Ideally, an anticancer drug target should be specific to cancer cells, in order to both increase efficacy and decrease toxicity of the compound.
Areas Covered In This Review:
Epithelial cell adhesion molecule (EpCAM) is a membrane protein with proto-oncogenic properties that is expressed in a number of endothelium-derived cancers and is a promising anticancer drug target. Adecatumumab is a monoclonal, fully human IgG1 antibody that targets EpCAM, development of which is at present reaching Phase III trials.
What The Reader Will Gain:
From a review of literature, we here update the rationale for using EpCAM as an anticancer target for monoclonal antibodies, with a special focus on adecatumumab. The fully human nature of adecatumumab is also discussed to put the drug in perspective with other related anti-EpCAM monoclonal antibodies, such as edrecolomab and catumaxomab. Adecatumumab studies are recapitulated, in order to provide the reader with a comprehensive view of the development of this promising anticancer agent.
Take Home Message:
Adecatumumab is a promising fully human monoclonal antibody targeting EpCAM which is expressed in almost all adenocarcinomas and its activity is not dependent of K-Ras status.
Insights
Adecatumumab is a fully human monoclonal antibody targeting EpCAM, a promising anticancer drug target. This antibody shows potential in treating adenocarcinomas, regardless of K-Ras status.
Area of Science:
- Oncology
- Immunology
- Drug Development
Background:
- Identifying cancer-specific drug targets is crucial for improving anticancer drug efficacy and reducing toxicity.
- Epithelial cell adhesion molecule (EpCAM) is a proto-oncogenic protein expressed in various cancers, making it a promising therapeutic target.
Purpose of the Study:
- To review the rationale for targeting EpCAM with monoclonal antibodies, focusing on adecatumumab.
- To provide a comprehensive overview of adecatumumab's development as an anticancer agent.
Main Methods:
- Literature review of EpCAM as an anticancer target.
- Analysis of adecatumumab, a fully human IgG1 antibody targeting EpCAM.
- Comparison with other anti-EpCAM antibodies (e.g., edrecolomab, catumaxomab).
Main Results:
- EpCAM is a validated target for monoclonal antibody therapy in cancer.
- Adecatumumab is a fully human antibody in late-stage clinical trials (Phase III).
- The efficacy of adecatumumab is not influenced by the K-Ras mutation status.
Conclusions:
- Adecatumumab represents a promising therapeutic strategy for adenocarcinomas.
- Its fully human nature may offer advantages over other anti-EpCAM antibodies.
- Targeting EpCAM is a viable approach for developing novel anticancer drugs.
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