Core E Radioimmunotherapy is designed to support Project I-Allogeneic Bone Marrow Transplantation for Hematologic Malignancy and Project II-Autologous Bone Marrow Transplantation for Hematologic Malignancy by providing the necessary reagents to accomplish allogeneic and autologous bone marrow transplantation utilizing radioimmunotherapy as one of the elements in the conditioning regimen. In addition to the production of the radiopharmaceutical Core E will also provide the required clinical physics to administer these reagents in a safe and efficacious manner. This Core will utilize three different monoclonal antibodies, one directed against CD33, one directed against CD20 and one directed CD45. The anti-CD45 monoclonal will be provided by the Fred Hutchinson Cancer Research Center and will be coupled to Iodine 131 for both dosimetry and therapy. The radiolabeling will be done at a commercial laboratory in order to facilitate expanded Phase II and Phase III studies. The anti-CD20 antibody will be prepared at the City of Hope National Medical Center where it will be conjugated to a novel macrocycle chelating agent prior to being radiolabeled with either Indium 111 fore imaging/dosimetry for Yttrium 90 for therapy. The anti-CD33 antibody will also be prepared at the City of Hope National Medical Center, being the first monoclonal to be produced at the Center for Biomedicine and Genetics (CBG) under the auspices of Core F- Biomedicine Production Core. Once purified the antibody will be conjugated to the aforementioned chelating agent for clinical trials. All radiolabeling of the anti-CD33 and anti-CD20 monoclonal antibodies will be accomplished in a clinical trials. All radiolabeling for the anti-CD33 and anti-CD20 monoclonal antibodies will be accomplished in a Radiopharmacy dedicated to the production of radiolabeled antibodies. After the radiolabeled antibodies are administered to the patients under the auspices of Project I and Project II, the patients undergo imaging in the Department of Nuclear Medicine to allow determination of the amount of radioactivity throughout the body to enable estimation of the deposition radiation doses. The clinical physics component of this core will then provide an estimation of the dose of Yttrium 90 to be administered to the patient to achieve the radiation doses defined in the various clinical protocols. In this was, the administered dose will be patient specific, delivered on a calculated target dose to specified organs rather than on a patient weight or body surface area. The clinical protocols developed in Project I and Project II will allow for the substitution of specific radioimmunotherapy for non-specific total body radiation currently utilized in similar clinical protocols. This novel method should afford more efficacious treatment will also assist in the development of the INDs covering the anti-CD33 and anti-CD20 monoclonal antibodies and their associated radioimmunoconjugates.
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