The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma

• Published in: Nature biotechnology Vol. 30; no. 7; pp. 631 - 637
• Main Authors: Senter, Peter D, Sievers, Eric L
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2012; Nature Publishing Group
• Subjects: 631/61/51/1568; 692/699/67/1059/602; 692/699/67/1990/291/1556; Agriculture; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - therapeutic use; Antigens, Neoplasm - immunology; Antineoplastic Agents - chemistry; Antineoplastic Agents - immunology; Antineoplastic Agents - therapeutic use; Bioinformatics; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Brentuximab vedotin; Cancer cells; Cancer therapies; Dosage and administration; Drug Discovery - trends; Drug therapy; Hodgkin Disease - drug therapy; Humans; Immunoconjugates - chemistry; Immunoconjugates - immunology; Immunoconjugates - therapeutic use; Life Sciences; Lymphoma; Lymphoma, Large-Cell, Anaplastic - drug therapy; Lymphomas; Molecular Targeted Therapy; Monoclonal antibodies; perspective; Pharmacokinetics; Pharmacology; Physiological aspects; Recurrence; Tumors; United States
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.2289

Progress has been made recently in developing antibody-drug conjugates (ADCs) that can selectively deliver cancer drugs to tumor cells. In principle, the idea is simple: by attaching drugs to tumor-seeking antibodies, target cells will be killed and nontarget cells will be spared. In practice, many parameters needed to be addressed to develop safe and effective ADCs, including the expression profiles of tumor versus normal tissues, the potency of the drug, the linker attaching the drug and placement of the drug on the antibody, and the pharmacokinetic and stability profiles of the resulting ADC. All these issues had been taken into account in developing brentuximab vedotin (Adcetris), an ADC that recently received accelerated approval by the US Food and Drug Administration for the treatment of relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL). Research is under way to extend the applications of brentuximab vedotin and to advance the field by developing other ADCs with new linker and conjugation strategies.