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| Grant Number: | 5R44CA085130-03 |
| PI Name: | FRITZBERG, ALAN R. |
| PI Email: | arfritz@neorx.com |
| PI Title: | |
| Project Title: | PRETARGETED RIT TO TREAT NON-HODGKIN'S LYMPHOMA |
Abstract: The objective of the proposed research is to develop a therapeutic agent based on pretarget radioimmunotherapy that is superior to the current treatments of non-Hodgkin's B-cell lymphoma in terms of therapeutic efficacy and non-target organ toxicity. Fusion proteins of a single chain antibody and streptavidin (scFv/SA) will be developed that are reactive with CD2O and target in a lymphoma xenograft animal model. Two candidate scFv/SA constructs will be genetically modified (e.g., with changes to the linker region) for the purpose of improving the expression, purification, and/or biochemical characteristics. Additional fusion constructs will be generated from selection of a human Fab/phage display library on CD2O-positive peripheral blood lymphocytes. All scFv/SA candidates will be evaluated for meeting set criteria for E. coli expression level, purification yield, immunoreactivity and CD2O cell binding, biotin binding affinity, and targeting ability in a lymphoma xenograft animal model. These characteristics should be sufficient to warrant further Phase II efforts directed toward cGMP scale-up and formulation development for clinical trials. PROPOSED COMMERCIAL APPLICATIONS: The application of radioimmunotherapy toward the treatment of non- Hodgkin's lymphoma (NHL) has been constrained by dose limiting toxicity to the radiosensitive bone marrow. Antibody pretargeting provides a method to specifically deliver significantly greater doses to tumor sites without serious toxicities. A large number of patients with NHL are candidate's for this treatment. These patients represent a sizable market opportunity.
Thesaurus Terms:
monoclonal antibody, neoplasm /cancer radioimmunotherapy, nonHodgkin's lymphoma
CD antigen, antigen antibody reaction, binding protein, biotin, chimeric protein, yttrium
clinical research, flow cytometry, human subject, laboratory mouse, protein purification
| Institution: | NEORX CORPORATION |
| 410 W HARRISON ST | |
| SEATTLE, WA 98119 | |
| Fiscal Year: | 2002 |
| Department: | |
| Project Start: | 15-JAN-2001 |
| Project End: | 31-DEC-2002 |
| ICD: | NATIONAL CANCER INSTITUTE |
| IRG: | ZRG1 |