Brentuximab vedotin

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Brentuximab vedotin (ADCETRIS®) targets CD30 using our proprietary antibody–drug conjugate (ADC) technology. CD30 is found on the surface of most classical Hodgkin lymphoma (HL) cells and in several types of non-Hodgkin lymphoma, but not commonly found on healthy cells.

This ADC therapy uses a linker system that is designed to be stable in the bloodstream and release a cytotoxic (cell-killing) agent once internalized into CD30-expressing cells, resulting in targeted cell death. Brentuximab vedotin is composed of an anti-CD30 monoclonal antibody and a cytotoxic agent, monomethyl auristatin E (MMAE), which are attached by a protease-cleavable linker.

Brentuximab vedotin is being developed in collaboration with Takeda Pharmaceutical Company.

Proposed mechanism of action of brentuximab vedotin and nivolumab

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Seagen medication brentuximab vedotin
Seagen medication brentuximab vedotin annotated
Seagen medication brentuximab vedotin
Seagen medication brentuximab vedotin annotated

This proposed mechanism is based on nonclinical data. Brentuximab vedotin is an investigational agent in this setting. Its safety and efficacy have not yet been established.

References

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  1. ADCETRIS [Prescribing Information]. Bothell, WA: Seagen, Inc. October 2019.
  2. Bossard et al. Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels. Blood. 2014;124:2983-2986.
  3. Wahl AF, et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease. Cancer Res. 2002;62(13):3736-3742.
  4. Francisco JA, et al. cAC10-vcMMAE, an anti-CD30–monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102(4):1458-1465.
  5. Doronina SO, et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol. 2003;21(7):778-784.
  6. Okeley NM, et al. Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res. 2010;16(3):888-897.
  7. Oflazoglu E, et al. Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30. Blood. 2007;110(13):4370-4372.
  8. Li F, et al. Tumor-Associated Macrophages Can Contribute to Antitumor Activity through FcγR-Mediated Processing of Antibody–Drug Conjugates. Mol Cancer Thera. 2017;6(7):1347-1354.
  9. Gardai SJ, et al. Cancer Res. 2015;75(15):Abstract 2469.
  10. Müller P, et al. Microtubule-depolymerizing agents used in antibody–drug conjugates induce antitumor immunity by stimulation of dendritic cells. Cancer Immunol Res. 2014;2(8):741-755.
  11. Vignali DA, et al. How regulatory T cells work. Nat Rev Immunol. 2008;8(7):523-532.
  12. Herrera AF, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018;131(11):1183-1194.
  13. Drake CG, et al. Mechanisms of immune evasion by tumors. Adv Immunol. 2006;90:51-81.
  14. Topalian SL, et al. Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med. 2013;366(26):2443-2454.