The aim of this work is to produce a clinically useful, commercially viable, new therapy agent against Non-Hodgkin's Lymphoma. Radioimmunotherapy has shown clinical efficacy against B-cell lymphoma in the last few years, and shows promise of becoming a completely new treatment modality for this disease. We will produce a Y-90 radiolabeled, humanized, anti-CD22 antibody, Y-90-hLL2, which can be practically manufactured, kit-formulated, radiolabeled and used. The product will take advantage of the internalizing properties of the hLL2 mab, bear a residualizing radiolabel, be designed with minimum potential for patient immune response, and ultimately, could be useful on an out-patient basis. Phase II work will determine the best option for the Y-90-hLL2 product from the several putative agents, by studying the properties of each with respect every aspect of the subject, including: Preparative ease, kit stability, radiolabeling efficiency, post-labeling product stability including radiolysis concerns, potential for immunogenicity, cellular binding/retention properties, animal pharmacokinetics, and clinical-use viability. From this, the chosen agent will be taken to a clinical phase I study to establish human targeting, dosimetry, the maximum tolerated dose of the agent, and preliminary efficacy. POTENTIAL COMMERCIAL APPLICATION: There are not good treatment options for patients with relapsed B-cell lymphoma, and patients are often stricken in their middle years, making societal costs heavy. This disease, of steadily increasing incidence, is responsive to radiation, including antibody-targeted radiation. If our advanced antibody-targeted yttrium-90 agent can be shown to have efficacy in this work against some of the sickest of patients, our agent could eventually find widespread application as a new, complementary modality. Then, use at an earlier, more responsive, disease stage may be feasible.
