Radioimmunotherapy of human B-cell chronic lymphocytic leukemia in nude mice

After i.v. or i.p. inoculation of 5 x 10(6) 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 microCi)-linked Dal B02 (50 micrograms/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 10(6) D10-1 cells. However, when the mice were treated 3 days after i.p. inoculation of 15 x 10(6) D10-1 cells, or 7 days after the i.v. inoculation of 5 x 10(6) 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 microCi) linked to 100 micrograms 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 microCi) linked to 50 micrograms of Dal B02 led to complete tumor cure in 3 of 4, mice, but two injections of 50 micrograms of unmodified Dal B02 had no effect on the s.c. xenografts. Two injections of 131I (500 microCI) linked to 100 micrograms of Dal B02 F(ab')2 fragment caused significant tumor inhibition but no tumor cure. 131I (300 microCi) linked to 50 micrograms 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.