Brentuximab vedotin (SGN-35)

Jessica Katz, John Edward Janik, Anas Younes

Research output: Contribution to journalReview article

210 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6428-6436
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number20
DOIs
StatePublished - Oct 15 2011

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Hodgkin Disease
Anaplastic Large-Cell Lymphoma
CD30 Antigens
cAC10-vcMMAE
Bystander Effect
Reed-Sternberg Cells
Citrulline
Tumor Microenvironment
Dipeptides
Valine
Regulatory T-Lymphocytes
Microtubules
Polymerization
Ligation
Intercellular Signaling Peptides and Proteins
Cell Death
Immunoglobulin G
Monoclonal Antibodies
monomethyl auristatin E
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Katz, J., Janik, J. E., & Younes, A. (2011). Brentuximab vedotin (SGN-35). Clinical Cancer Research, 17(20), 6428-6436. https://doi.org/10.1158/1078-0432.CCR-11-0488

Brentuximab vedotin (SGN-35). / Katz, Jessica; Janik, John Edward; Younes, Anas.

In: Clinical Cancer Research, Vol. 17, No. 20, 15.10.2011, p. 6428-6436.

Research output: Contribution to journalReview article

Katz, J, Janik, JE & Younes, A 2011, 'Brentuximab vedotin (SGN-35)', Clinical Cancer Research, vol. 17, no. 20, pp. 6428-6436. https://doi.org/10.1158/1078-0432.CCR-11-0488
Katz, Jessica ; Janik, John Edward ; Younes, Anas. / Brentuximab vedotin (SGN-35). In: Clinical Cancer Research. 2011 ; Vol. 17, No. 20. pp. 6428-6436.
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