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Comparison of a tetravalent single-chain antibody-streptavidin fusion protein and an antibody-streptavidin chemical conjugate for pretargeted anti-CD20 radioimmunotherapy of B-cell lymphomas
| Content Provider | Scilit |
|---|---|
| Author | Pagel, John M. Lin, Yukang Hedin, Nathan Pantelias, Anastasia Axworthy, Donald Stone, Diane Hamlin, Don K. Wilbur, D. Scott |
| Copyright Year | 2006 |
| Description | The efficacy of radioimmunotherapy (RIT) for patients with relapsed non-Hodgkin lymphoma (NHL) is limited by nonspecific delivery of radiation to normal tissues due to the long circulating half-life of radiolabeled anti-CD20 antibodies (Abs). Pretargeted RIT using a covalent conjugate of the 1F5 anti-CD20 Ab with streptavidin (SA) has been shown to augment the efficacy of RIT and decrease toxicity compared with a directly labeled 1F5 Ab. We have engineered a tetravalent singlechain 1F5 (scFv)4SA fusion protein and compared it to the 1F5-SA conjugate. Athymic mice bearing Ramos lymphoma xenografts received either the conjugate or fusion protein, followed 20 hours later by a biotin-N-acetyl-galactosamine clearing agent, followed 4 hours later by 111In-DOTA-biotin. After 24 hours, 11.4% ± 2.1% of the injected dose of radionuclide was present per gram of tumor (% ID/g) using 1F5 (scFv)4SA compared with 10.8% ± 2.5% ID/g with 1F5 Ab-SA. Superior tumor-to-normal organ ratios of radioactivity were consistently seen using the fusion protein compared with the chemical conjugate (eg, tumor-to-blood ratio > 65:1 after 48 hours with the fusion protein, but < 7:1 with the conjugate). More than 90% of lymphomabearing mice could be cured with minimal toxicity using either reagent followed by 1200 μCi (44.4 MBq) 90Y-DOTA-biotin. (Blood. 2006;108:328-336) |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895842/pdf |
| Ending Page | 336 |
| Page Count | 9 |
| Starting Page | 328 |
| DOI | 10.1182/blood-2005-11-4327 |
| Journal | Blood |
| Issue Number | 1 |
| Volume Number | 108 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2006-07-01 |
| Access Restriction | Open |
| Subject Keyword | Hematology Biotin Radioimmunotherapy Acetyl Hodgkin Lymphoma Antibody Mice Anti Cd20 Streptavidin Journal: Blood (Vol- 16, Issue- 1) |
| Content Type | Text |
| Resource Type | Article |
