Abstract
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.
Original language | English (US) |
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Pages (from-to) | 11-23 |
Number of pages | 13 |
Journal | Cancer Biotherapy and Radiopharmaceuticals |
Volume | 19 |
Issue number | 1 |
DOIs | |
State | Published - 2004 |
Keywords
- Anti-CD19
- Bone marrow transplantation
- Leukemia
- Nude mice
- Radioimmunoconjugate
- Radiopharmaceutical
- Tumor
- Y
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Pharmacology
- Cancer Research