Brentuximab Vedotin (SGN-35).

Abstract

Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) directed against the CD30 antigen expressed on Hodgkin lymphoma and anaplastic large cell lymphoma. SGN-35 consists of the cAC10 chimerized IgG1 monoclonal antibody SGN30, modified by the addition of a valine-citrulline dipeptide linker to permit attachment of the potent inhibitor of microtubule polymerization monomethylauristatin E (MMAE). In phase II trials, SGN-35 produced response rates of 75% in patients with Hodgkin lymphoma (n = 102) and 87% in patients with anaplastic large cell lymphoma (n = 30). Responses to SGN-35 might be related not only to the cytotoxic effect due to release of MMAE within the malignant cell but also to other effects. First, SGN-35 may signal malignant cells through CD30 ligation to deliver an apoptotic or proliferative response. The former would amplify the cytotoxicity of MMAE. A proliferative signal delivered in the context of MMAE intoxication could enhance cell death. Second, the efficacy of SGN-35, particularly in Hodgkin lymphoma, might be attributed to its effect on the tumor microenvironment. Diffusion of free MMAE from the targeted tumor cells could result in a bystander effect that kills the normal supporting cells in close proximity to the malignant cells. The elimination of T regulatory cells that inhibit cytotoxic effector cells and elimination of cells that provide growth factor support for Hodgkin/Reed-Sternberg cells could further enhance the cytotoxic activity of SGN-35. Here we review the biology of SGN-35 and the clinical effects of SGN-35 administration.

• Authors: Jessica Katz, John E Janik, Anas Younes
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 20 Pg. 6428-36 (Oct 15 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 22003070 (Publication Type: Journal Article)
• Copyright: ©2011 AACR.

Chemical References

• Antineoplastic Agents
• Immunoconjugates
• Ki-1 Antigen
• Brentuximab Vedotin

Topics

• Antineoplastic Agents (therapeutic use)
• Brentuximab Vedotin
• Clinical Trials as Topic
• Hodgkin Disease (drug therapy)
• Humans
• Immunoconjugates (therapeutic use)
• Ki-1 Antigen (immunology)
• Lymphoma, Large-Cell, Anaplastic (drug therapy)