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

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 °Ci)-linked Dal B02 (50 ug/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, 13,I-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 uCi) linked to 100 ug 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 °Ci) linked to 50 ug of Dal B02 led to complete tumor cure in 3 of 4 mice, but two injections of 50 g of unmodified Dal B02 had no effect on the s.c. xenografts. Two injections of 131I (500 °Ci) linked to 100 g of Dal B02 F(ab’)2 fragment caused significant tumor inhibition but no tumor cure. 131I (300 uCi) linked to 50 ug of a nonspecific IgGl only led to minor tumor inhibition. A mixture of unmodified Dal B02 and 131I-linked nonspecific IgGl was not a more potent tumor inhibitor than the 131I-linked nonspecific IgGl 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.