The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma.
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.
Seattle Genetics, Bothell, Washington, USA. psenter@seagen.com
Peter D
PD
Senter
Eric L
EL
Sievers
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D000079963:Brentuximab Vedotin; D055808:Drug Discovery / Q000639:trends; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D012008:Recurrence
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D000079963:Brentuximab Vedotin