title: Histone deacetylase inhibition enhances the lymphomacidal activity of the anti-CD22 monoclonal antibody HB22.7.
abstract: HB22.7, an anti-CD22 monoclonal antibody has shown consistent preclinical activity against non-Hodgkin lymphoma (NHL). Histone deacetylase inhibitors (HDACi) have demonstrated efficacy in lymphoma and can modulate cell surface receptor expression. To augment the lymphomacidal activity of HB22.7 we examined the combination of AR42 (an HDACi) and HB22.7 in vitro and in vivo. The combination resulted in 10-fold increased potency in 6 NHL cell lines when compared to either drug alone. Both drugs reduced tumor progression in xenografts, but the combination was significantly more efficacious and resulted in regression of established tumors, without toxicity. AR42 inhibited HB22.7-mediated CD22 internalization, suggesting that increased efficacy could be due to higher availability of CD22. Overall, the synergistic effects of HB22.7 and AR42 on in vitro cytotoxicity and in vivo anti-tumor activity make this combination an attractive option for further pre-clinical and clinical evaluation.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA; Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: YanGuo
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Barisone
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: Mastewal
authors.initials: M
authors.lastname: Abuhay
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA; Department of Veterans' Affairs, Northern California Healthcare System, Sacramento, CA, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: O'Donnell
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: Zaneb
authors.initials: Z
authors.lastname: Buksh
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: Faraz
authors.initials: F
authors.lastname: Yousefian
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA; Department of Veterans' Affairs, Northern California Healthcare System, Sacramento, CA, USA. Electronic address: joseph.tuscano@ucdmc.ucdavis.edu.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Tuscano
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; C497867:CD22 protein, human; D056572:Histone Deacetylase Inhibitors; D051918:Sialic Acid Binding Ig-like Lectin 2
keywords: AR42; Anti-cancer drugs; CD22; HB22.7; Lymphoma; NHL