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.
O'Donnell
Robert T
RT
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
Ma
Yunpeng
Y
McKnight
Hayes C
HC
Pearson
David
D
Tuscano
Joseph M
JM
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