ブレンツキシマブ　ベドチン（遺伝子組換え）

ブレンツキシマブ　ベドチン（遺伝子組換え） 化学特性,用途語,生産方法

• 説明

  Brentuximab verdotin was approved by the U.S. FDA in August 2011 for treatment of Hodgkin’s lymphoma (HL) in patients who have failed autologous stem cell transplant (ASCT) or ASCT ineligible patients who have failed at least two prior chemotherapy regimens, and for second line treatment of systemic anaplastic large cell leukemia (ALCL). Brentuximab verdotin is a chimeric (mouse V region/human C region) CD30 binding monoclonal antibody (cAC10) that is conjugated via cysteine residues to a small molecule comprising a cysteine reactive dipeptide linker moiety and the microtubule polymerization inhibitor monomethyl auristatin E(MMAE). The antibody component of the drug binds to CD30 expressing tumor cells, and the active cytotoxic component, MMAE, is released by proteolytic cleavage of the dipeptide linker moiety.

• 臨床応用

  Brentuximab vedotin is an antibody drug conjugate that is comprised of an anti-CD30 antibody and the potent tubulin based inhibitor monomethyl auristatin E (MMAE). These two entities are connected together via a linker consisting of a maleimide conjugation handle that includes an enzyme-cleavable valine-citrulline- para-aminobenzylcarbamate group. This conjugation handle releases MMAE after internalization of the conjugate by the cancer cell that recognizes the antibody. Brentuximab vedotin was discovered by Seattle Genetics who co-developed the conjugate with Millenium Pharmaceuticals. Brentuximab vendotin has been approved for the treatment of relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) and relapsed or refractory Hodgkin’s lymphoma. Brentuximab vedotin is also undergoing clinical trials for the treatment of CD30-expressing cutaneous T-cell lymphoma and CD30-positive hematologic malignancies. Although brentuximab vedotin is classified as a biologic, an exception has been made to include it in this year’s review because the small molecule portion of the conjugate was prepared by total synthesis.

ブレンツキシマブ　ベドチン（遺伝子組換え） 生産企業

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