Histone deacetylase inhibition enhances the lymphomacidal activity of the anti-CD22 monoclonal antibody HB22.7

• We propose that AR42 enhances HB22.7's efficacy by increasing CD22 surface levels.
• HB22.7 and AR42 showed synergistic lymphomacidal activity in vitro and in vivo.
• AR42 inhibited HB22.7-mediated CD22 internalization.
• HB22.7 with HDAC inhibition may be a safe and efficacious NHL therapy.

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.