title: The HB22.7-vcMMAE antibody-drug conjugate has efficacy against non-Hodgkin lymphoma mouse xenografts with minimal systemic toxicity.
abstract: 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.
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, UCDHS 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
authors: Mastewal
authors: M
authors: Abuhay
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, UCDHS 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
authors: Jason
authors: J
authors: Kato
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, UCDHS 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
authors: Emily
authors: E
authors: Tuscano
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, UCDHS 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
authors: Gustavo A
authors: GA
authors: Barisone
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, UCDHS 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
authors: Ranjit S
authors: RS
authors: Sidhu
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, UCDHS 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.|Department of Veterans' Affairs, Northern California Healthcare System, Mather, CA, USA.
authors: Robert T
authors: RT
authors: O'Donnell
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, UCDHS 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA. joseph.tuscano@ucdmc.ucdavis.edu.|Department of Veterans' Affairs, Northern California Healthcare System, Mather, CA, USA. joseph.tuscano@ucdmc.ucdavis.edu.
authors: Joseph M
authors: 0000-0002-0522-1406
authors: JM
authors: Tuscano
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D000922:Immunotoxins / Q000737:chemistry / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D009842:Oligopeptides / Q000737:chemistry / Q000627:therapeutic use*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D009842:Oligopeptides; D051918:Sialic Acid Binding Ig-like Lectin 2; C495575:monomethyl auristatin E
keywords: Antibody–drug conjugate; CD22; HB22.7; Lymphoma; MMAE; NHL