Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts.
CD22 is a cell-surface adhesion molecule on most B-cell NHL, so it is a promising target for immunotherapy. HB22.7 is an anti-CD22 mAb that binds the two NH(2)-terminal immunoglobulin domains and specifically blocks the interaction of CD22 with its ligand. CD22-blocking mAbs induce apoptosis in neoplastic B-cells and are functionally distinguishable from other anti-CD22 mAbs. This study assessed the optimal dose, route, schedule, and the targeted CD22 epitope. Raji NHL-bearing nude mice were studied. A non-blocking anti-CD22 mAb (HB22.27) was used as a control. HB22.27 had minimal effect, whereas HB22.7 improved survival and shrank tumors substantially. HB22.7 doses greater than 1.4 mg/week did not further increase efficacy (or toxicity). Tumors less than 200 mm(3) had a higher response rate than did larger tumors. Various schedules of HB22.7 administration were tested; one dose every other week was more effective than more or less frequent dosing. Pharmacokinetic studies revealed that the half-life of HB22.7 was 28 days; this correlated with the time needed to re-populate cell-surface CD22 after treatment with HB22.7. Immuno-PET showed that NHL was rapidly and specifically targeted by copper-64-labeled-HB22.7. This study provided data as to an optimal dose, route, schedule and interval between doses of HB22.7.
Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis, Cancer Center, Suite 3016, Sacramento, CA 95817, USA. robert.odonnell@ucdmc.ucdavis.edu
Robert T
RT
O'Donnell
Yunpeng
Y
Ma
Hayes C
HC
McKnight
David
D
Pearson
Joseph M
JM
Tuscano
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000939:Epitopes; D051918:Sialic Acid Binding Ig-like Lectin 2