Combined Modality Radioimmunotherapy with Taxol and 90Y-LYM-1 for Raji Lymphoma Xenografts

Abstract

Despite effective therapies for non-Hodgkin's lymphoma (NHL), the majority of patients are not cured. Radioimmunotherapy (RIT) has shown good results in preclinical and clinical trials even in patients that are non-responsive to standard chemotherapy. To make RIT more effective, agents such as paclitaxel (Taxol), that can enhance radiation effects, are being tested. Nude mice bearing human Burkitt's lymphoma (Raji) xenografts were treated with: 1) 150 or 200 μCi (5.5 or 7.3 MBq) of⁹⁰Y-2IT-BAD-Lym-l alone, 2) 600 μg of Taxol alone, 3) 150 or 200 μCi of⁹⁰Y-2IT-BAD-Lym-l plus 600 μg of Taxol given 24 hours after RLT, or 4) no treatment. Tumor size, survival, mouse weight and blood counts were monitored to assess efficacy and toxicity. Survival for mice treated in this 84 day trial was: 71% for ⁹⁰Y-2IT-BAD-Lym-1 (200 μCi) plus Taxol, 29% for Taxol alone, 6% for ⁹⁰Y-2IT-BAD-Lym-1 (200 μCi) alone and 14% in the untreated group. Average tumor volume in the ⁹⁰Y-2IT-BAD-Lym-l (200 μCi) plus Taxol group was reduced by 89 and 99% compared to the RLT alone and Taxol alone groups, respectively. Mice treated with 150 μCi had less toxicity than those treated with 200 μCi of⁹⁰Y-2IT-BAD-Lym-l, however, the higher radiation dose, and Taxol, were required for improved survival. Mouse weights and myelotoxicity in the combined modality (RLT plus Taxol) groups were similar to those receiving the same dose of RIT alone. In the Raji tumored nude mouse model, addition of Taxol to ⁹⁰Y-2IT-BAD-Lym-1, in doses clinically achievable in humans, provided therapeutic synergy without increased or excessive toxicity.