The HB22.7–vcMMAE antibody–drug conjugate has efficacy against non-Hodgkin lymphoma mouse xenografts with minimal systemic toxicity

详细信息    查看全文

• 作者：Mastewal Abuhay ; Jason Kato ; Emily Tuscano…
• 关键词：HB22.7 ; Lymphoma ; Antibody–drug conjugate ; MMAE ; CD22 ; NHL
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：65
• 期：10
• 页码：1169-1175
• 全文大小：590 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851
• 卷排序：65

文摘

In this study, HB22.7, an anti-CD22 monoclonal antibody, was used for specific, targeted delivery of monomethyl auristatin E (MMAE) to non-Hodgkin lymphoma (NHL). MMAE was covalently coupled to HB22.7 through a valine–citrulline peptide linker (vc). Maleimide-functionalized vcMMAE (mal-vcMMAE) was reacted with thiols of the partially reduced mAb. Approximately 4 molecules of MMAE were conjugated to HB22.7 as determined by residual thiol measurement and hydrophobic interaction chromatography–HPLC (HIC-HPLC). HB22.7–vcMMAE antibody–drug conjugate (ADC) retained its binding to Ramos NHL cells and also exhibited potent and specific in vitro cytotoxicity on a panel of B cell NHL cell lines with IC₅₀s of 20–284 ng/ml. HB22.7–vcMMAE also showed potent efficacy in vivo against established NHL xenografts using the DoHH2 and Granta 519 cell lines. One dose of the ADC induced complete and persistent response in all DoHH2 xenografts and 90 % of Granta xenografts. Minimal toxicity was observed. In summary, HB22.7–vcMMAE is an effective ADC that should be evaluated for clinical translation.