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Radioimmunotherapy of Human B-Cell Chronic Lymphocytic Leukemia in Nude Mice¹

Departments of Pathology [Z. Z., T. G., C. L. Y. L., M. M.], Microbiology and Immunology [Z. Z., D. H., S. H. S.], and Medicine [L. A. F.], Dalhousie University, Nova Scotia, Canada B3H 4H7

After i.v. or i.p. inoculation of 5 x 10⁶ D10-1 cells, a subclone of an Epstein-Barr virus transformed human B-cell chronic lymphocytic leukemia (CLL) line, 100% of nude mice developed solid or ascites tumors and died within 17–60 days of tumor inoculation. There was significant tumor inhibition, including tumor cure, when these tumor-inoculated mice were treated with either unmodified or ¹³¹I (300 µCi)-linked Dal B02 (50 µg/mouse), a monoclonal antibody directed against surface-associated antigens on human CLL B-cells and several histological types of B-lymphoma cells. There was no significant difference between the antitumor activity of unmodified Dal B02 and ¹³¹I-linked Dal B02 when the treatment was given 3 days after i.p. or i.v. inoculation of 5 x 10⁶ D10-1 cells. However, when the mice were treated 3 days after i.p. inoculation of 15 x 10⁶ D10-1 cells, or 7 days after the i.v. inoculation of 5 x 10⁶ D10-1 cells, ¹³¹I-linked Dal B02 was a more potent tumor inhibitor than was unmodified Dal B02 (P < 0.05 and P < 0.01, respectively). Two injections of ¹³¹I (500 µCi) linked to 100 µg of a Dal B02 F(ab')₂ fragment preparation also prolonged the survival of i.p. or i.v. tumor-inoculated mice (P < 0.05 and P = 0.05, respectively). In nude mice with established s.c. xenografts of D10-1 cells, two injections of ¹³¹I (300 µCi) linked to 50 µg of Dal B02 led to complete tumor cure in 3 of 4 mice, but two injections of 50 µg of unmodified Dal B02 had no effect on the s.c. xenografts. Two injections of ¹³¹I (500 µCi) linked to 100 µg of Dal B02 F(ab')₂ fragment caused significant tumor inhibition but no tumor cure. ¹³¹I (300 µCi) linked to 50 µg of a nonspecific IgG1 only led to minor tumor inhibition. A mixture of unmodified Dal B02 and ¹³¹I-linked nonspecific IgG1 was not a more potent tumor inhibitor than the ¹³¹I-linked nonspecific IgG1 preparation by itself. These results suggest that Dal B02 may be an effective carrier for the radioimmunotherapy of human B-cell CLL and other appropriate B-cell lymphomas, especially in the progressive phase of B-cell CLL, which is usually not amenable to currently available therapeutic modalities.

¹ This study was supported by Grant 10964 from the Medical Research Council of Canada and the Cancer Research Society, Inc., Montreal, Canada.

² Present address: Department of Cell Genetics, Genentech, Inc., 460 Point San Bruno Blvd., South San Francisco, CA 94080.

³ To whom requests for reprints should be addressed, at Department of Pathology, Sir Charles Tupper Medical School, College Street, Halifax, Nova Scotia, B3H 4H7, Canada.

Received 7/29/94. Accepted 8/ 3/94.

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