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

Autor: Emily Tuscano, Gustavo A. Barisone, Mastewal Abuhay, Jason Kato, Robert T. O'Donnell, Ranjit S. Sidhu, Joseph Tuscano
Rok vydání: 2016
Předmět:
0301 basic medicine
Cancer Research
Lymphoma
Sialic Acid Binding Ig-like Lectin 2
Apoptosis
Mice
SCID
Mice
chemistry.chemical_compound
0302 clinical medicine
hemic and lymphatic diseases
Monoclonal
Immunology and Allergy
Cancer
Mice
Inbred ICR
B-Lymphocytes
HB22.7
Tumor
Chemistry
Lymphoma
Non-Hodgkin
Immunotoxins
CD22
Antibodies
Monoclonal
Hematology
Inbred ICR
medicine.anatomical_structure
Oncology
Monomethyl auristatin E
5.1 Pharmaceuticals
030220 oncology & carcinogenesis
Female
Immunotherapy
MMAE
Development of treatments and therapeutic interventions
Oligopeptides
Antibody–drug conjugate
Biotechnology
Antibody-drug conjugate
medicine.drug_class
Immunology
Non-Hodgkin
SCID
Monoclonal antibody
NHL
Article
Antibodies
Cell Line
03 medical and health sciences
Rare Diseases
In vivo
Cell Line
Tumor
medicine
Animals
B cell
medicine.disease
Xenograft Model Antitumor Assays
Virology
Orphan Drug
030104 developmental biology
Cancer research
Conjugate
Zdroj: Cancer immunology, immunotherapy : CII, vol 65, iss 10
Cancer Immunol Immunother
ISSN: 1432-0851
0340-7004
DOI: 10.1007/s00262-016-1873-y
Popis: In this study, the HB22.7 anti-CD22 mAb, was used for specific, targeted delivery of the potent anti-cancer agent, 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 IC(50)s 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.
Databáze: OpenAIRE
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