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A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts
| Content Provider | Scilit |
|---|---|
| Author | Corcoran, Melissa Subbiah, Krishnan Hamlin, Don K. Wilbur, D. Scott Johnson, Timothy Theodore, Louis Yau, Eric Mallett, Robert Meyer, Damon L. Axworthy, Don |
| Copyright Year | 2001 |
| Description | Radioimmunotherapy with anti-CD20 monoclonal antibodies is a promising new treatment approach for patients with relapsed B-cell lymphomas. However, the majority of patients treated with conventional radiolabeled anti-CD20 antibodies eventually have a relapse because the low tumor-to-blood and tumor-to–normal organ ratios of absorbed radioactivity limit the dose that can be safely administered without hematopoietic stem cell support. This study assessed the ability of a streptavidin-biotin “pretargeting” approach to improve the biodistribution of radioactivity in mice bearing Ramos lymphoma xenografts. A pretargeted streptavidin-conjugated anti-CD20 1F5 antibody was infused, followed 24 hours later by a biotinylated N-acetylgalactosamine–containing “clearing agent” and finally 3 hours later by 111In-labeled DOTA-biotin. Tumor-to-blood ratios were 3:1 or more with pretargeting, compared with 0.5:1 or less with conventional 111In-1F5. Tumor-to–normal organ ratios of absorbed radioactivity up to 56:1 were observed with pretargeting, but were 6:1 or less with conventional 111In-1F5. Therapy experiments demonstrated that 400 μCi (14.8 MBq) or more of conventional 90Y-1F5 was required to obtain major tumor responses, but this dose was associated with lethal toxicity in 100% of mice. In marked contrast, up to 800 μCi (29.6 MBq)90Y-DOTA-biotin could be safely administered by the pretargeting approach with only minor toxicity, and 89% of the mice were cured. These data suggest that anti-CD20 pretargeting shows great promise for improving current therapeutic options for B-cell lymphomas and warrants further preclinical and clinical testing. |
| Related Links | http://www.bloodjournal.org/content/bloodjournal/98/8/2535.full.pdf |
| Ending Page | 2543 |
| Page Count | 9 |
| Starting Page | 2535 |
| DOI | 10.1182/blood.v98.8.2535 |
| Journal | Blood |
| Issue Number | 8 |
| Volume Number | 98 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2001-10-15 |
| Access Restriction | Open |
| Subject Keyword | Hematology Research and Experimental Medicine Hematopoietic Antibodies Cd20 Pretargeting Lymphoma Xenografts Dota Biotin Normal Organ Organ Ratios Absorbed Radioactivity Journal: Blood (Vol- 104, Issue- 8) |
| Content Type | Text |
| Resource Type | Article |
