The CD22 Epitope, Dose, Dosing Interval, and Timing All Effect Efficacy of Anti-CD22 mAb-Based Therapy of NHL.

Rituximab, a chimeric anti-CD20 monoclonal antibody (mAb) has become integral to non-Hodgkins lymphoma therapy. New, clinically effective, anti-NHL mAb may further improve outcomes. CD22 is a B-lymphocyte-specific adhesion molecule on the surface of most NHL, so it is a promising target for immunotherapy. A panel of anti-CD22 mAbs were developed and tested. Anti-CD22 mAbs that bind the two NH₂-terminal immunoglobulin domains of CD22 and specifically block the interaction of CD22 with its ligand were identified. CD22-blocking mAbs induce apoptosis in neoplastic B-cells and are functionally distinguishable from other anti-B-cell, and even other anti-CD22 mAbs. MAbs that do not block ligand-binding have only modest functional effects. HB22.7 is the blocking anti-CD22 mAb chosen for study and characterization in a Raji NHL-bearing nude mouse model. The goal of this study was to characterize the dose, route and schedule of administration that can guide the translation of HB22.7 to a clinical trial. In addition to untreated Raji-bearing nude mice, a control, non-blocking mAb (HB22.27) was compared to HB22.7. The non-blocking mAb had minimal pre-clinical efficacy, whereas HB22.7 improved survival and caused substantial tumor shrinkage. Varying doses of HB22.7 were tested; doses greater than 1.4 mg did not further increase efficacy (or toxicity). An important consideration regarding translation of HB22.7 to clinical trials is the size of tumors to be treated. In this study, tumors less than 200 mm³ had a much higher response rate than did larger tumors. Varying schedules of HB22.7 administration (1.4 mg/dose) were tested; one dose every other week was more effective than more or less frequent dosing. Immuno-PET showed that NHL was effectively and specifically targeted when copper-64-labeled HB22.7 was administered either intravenously or subcutaneously. This study provided preclinical data as to a useful dose, route and schedule of administration of the anti-CD22 mAb, HB22.7