Trends in cancer-targeted antibody-drug conjugates.
Better knowledge of engineered antibodies and tumour biology has led to the development of novel targeted therapies, such as antibody-drug conjugates (ADCs). ADCs combine a monoclonal antibody, directed toward specific antigen highly expressed on the cancer cell, to potent cytotoxic drug through a stable linker. ADCs are designed to bind selectively to cancer cells and to deliver cytotoxic drugs into the cancer cell, which may preserve normal cells. ADCs should be stable and non-toxic in circulation. Upon binding to antigen, ADCs are internalized by different processes, followed by the intracellular release of an active form of the cytotoxic drug, which in turn kills the cancer cell. This technology has the potential to further improve the anticancer activity while limiting toxicity. First results from ongoing clinical trials are encouraging. Favourable pharmacokinetic profile was observed showing good stability in circulation. Clinical studies demonstrated that ADCs provide clinical efficacy with an acceptable safety profile. Objective responses and clinical benefits were demonstrated with the investigated ADCs. Major toxicities frequently associated to chemotherapy were barely or not reported with ADCs. Taken together, ADCs may become the new wave of anticancer drugs in the future.
Department of Medical Oncology, Institut Curie, Paris, France.
François-Clément
FC
Bidard
Olivier
O
Trédan
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D024201:Bystander Effect; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015394:Molecular Structure; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D009369:Neoplasms / Q000188:drug therapy*; D021381:Protein Transport
D000906:Antibodies; D000970:Antineoplastic Agents; D018796:Immunoconjugates