Radiotherapy of CD19 expressing Daudi tumors in nude mice with Yttrium-90-labeled anti-CD19 antibody.
Studies were performed to determine the suitability of using two different anti-CD19 monoclonal antibodies to deliver the high energy beta-particle emitting isotope 90Y to B-cell lymphoma grown as flank tumors in athymic nude mice. The antibodies BU12 and HD37, both of the IgG1 subclass, recognize CD19, an internalizing B-lineage-specific membrane glycoprotein and member of the Ig supergene family. The antibodies were readily labeled with 90Y using the highly stable chelate, 1B4M-MX-DTPA. The radioimmunoconjugates selectively bound to the CD19 expressing B cell line Daudi, but not to CD19 negative control cells. Significantly more 90Y anti-CD19 bound to Daudi tumors growing in nude mice than did a control non-binding antibody (p = 0.001). The biodistribution data correlated with an anti-tumor effect. Anti-tumor activity was dose dependent and the best results were observed in mice receiving a single dose of approximately 300 uCi. The anti-CD19 antibody had significantly better anti-tumor activity as compared to a control 90Y-labeled antibody and most mice survived over 119 days with no evidence of tumor (p < 0.003). Histology studies showed no significant injury to the kidney, liver, or small intestine. Because radiolabeled anti-CD19 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data support the use of 90Y anti-CD19 antibodies in treating B-cell malignancies.
Vallera
Daniel A
DA
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Cancer Center, Minneapolis, MN, USA. valle001@tc.umn.edu
Elson
Michael
M
Brechbiel
Martin W
MW
Dusenbery
Kathryn E
KE
Burns
Linda J
LJ
Jaszcz
Waclaw B
WB
Ramsay
Norma K
NK
Panoskaltsis-Mortar
Angela
A
Kuroki
David W
DW
Wagner
John E
JE
Vitetta
Ellen S
ES
Kersey
John H
JH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000915:Antibody Affinity; D018941:Antigens, CD19 / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D006801:Humans; D007205:Indium Radioisotopes; D051379:Mice; D008819:Mice, Nude; D011485:Protein Binding; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes