Combined modality radioimmunotherapy with taxol and 90Y-Lym-1 for Raji lymphoma xenografts

Robert T O'Donnell, Sally J. DeNardo, Laird A. Miers, David L. Kukis, Gary R. Mirick, Linda A. Kroger, Gerald L Denardo

Research output: Contribution to journalArticle

25 Citations (Scopus)

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) of 90Y-2IT-BAD-Lym-1 alone, 2) 600 μg of Taxol alone, 3) 150 or 200 μCi of 90Y-2IT-BAD-Lym-1 plus 600 μg of Taxol given 24 hours after RIT, 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-1 (200 μCi) plus Taxol group was reduced by 89 and 99% compared to the PIT alone and Taxol alone groups, respectively. Mice treated with 150 μCi had less toxicity than those treated with 200 μCi of 90Y-2IT-BAD-Lym-1, however, the higher radiation dose, and Taxol, were required for improved survival. Mouse weights and myelotoxicity in the combined modality (RIT 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.

Original languageEnglish (US)
Pages (from-to)351-361
Number of pages11
JournalCancer Biotherapy and Radiopharmaceuticals
Volume13
Issue number5
StatePublished - 1998

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Radioimmunotherapy
Paclitaxel
Heterografts
Lymphoma
Nude Mice
Survival
Weights and Measures
Burkitt Lymphoma
Radiation Effects
2IT-BAD-Lym-1 monoclonal antibody
Tumor Burden
Non-Hodgkin's Lymphoma
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Combined modality radioimmunotherapy with taxol and 90Y-Lym-1 for Raji lymphoma xenografts. / O'Donnell, Robert T; DeNardo, Sally J.; Miers, Laird A.; Kukis, David L.; Mirick, Gary R.; Kroger, Linda A.; Denardo, Gerald L.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 13, No. 5, 1998, p. 351-361.

Research output: Contribution to journalArticle

O'Donnell, Robert T ; DeNardo, Sally J. ; Miers, Laird A. ; Kukis, David L. ; Mirick, Gary R. ; Kroger, Linda A. ; Denardo, Gerald L. / Combined modality radioimmunotherapy with taxol and 90Y-Lym-1 for Raji lymphoma xenografts. In: Cancer Biotherapy and Radiopharmaceuticals. 1998 ; Vol. 13, No. 5. pp. 351-361.
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AU - Mirick, Gary R.

AU - Kroger, Linda A.

AU - Denardo, Gerald L

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AB - 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) of 90Y-2IT-BAD-Lym-1 alone, 2) 600 μg of Taxol alone, 3) 150 or 200 μCi of 90Y-2IT-BAD-Lym-1 plus 600 μg of Taxol given 24 hours after RIT, 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-1 (200 μCi) plus Taxol group was reduced by 89 and 99% compared to the PIT alone and Taxol alone groups, respectively. Mice treated with 150 μCi had less toxicity than those treated with 200 μCi of 90Y-2IT-BAD-Lym-1, however, the higher radiation dose, and Taxol, were required for improved survival. Mouse weights and myelotoxicity in the combined modality (RIT 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.

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