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 le ukemia (CLL) line, 100% of nude mice developed solid or ascites tumors and died within 17-60 days of tumor inoculation. There was significan t tumor inhibition, including tumor cure, when these tumor-inoculated mice were treated with either unmodified or I-131 (300 mu Ci)-linked D al B02 (50 mu g/mouse), a monoclonal antibody directed against surface -associated antigens on human CLL B-cells and several histological typ es of Blymphoma cells. There was no significant difference between the antitumor activity of unmodified Dal B02 and I-131-linked Dal B02 whe n 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. in oculation of 5 x 10(6) D10-1 cells, I-131-linked Dal B02 was a more po tent tumor inhibitor than was unmodified Dal B02 (P < 0.05 and P < 0.0 1, respectively). Two injections of I-131 (500 mu Ci) linked to 100 mu g of a Dal B02 F(ab')(2) fragment preparation also prolonged the surv ival of i.p. or i.v. tumor-inoculated mice (P < 0.05 and P = 0.05, res pectively). In nude mice with established s.c. xenografts of D10-1 cel ls, two injections of I-131 (300 mu Ci) linked to 50 pg of Dal B02 led to complete tumor cure in 3 of 4 mice, but two injections of 50 mu g of unmodified Dal B02 had no effect on the s.c. xenografts. Two inject ions of I-131 (500 mu Ci) linked to 100 pg of Dal B02 P(ab')(2) fragme nt caused significant tumor inhibition but no tumor cure. I-131 (300 m u Ci) linked to 50 mu g of a nonspecific IgG1 only led to minor tumor inhibition. A mixture of unmodified Dal B02 and I-131-linked nonspecif ic IgG1 was not a more potent tumor inhibitor than the I-131-linked no nspecific IgG1 preparation by itself. These results suggest that Dal B 02 may be an effective carrier for the radioimmunotherapy of human B-c ell CLL and other appropriate B-cell lymphomas, especially in the prog ressive phase of B-cell CLL, which is usually not amenable to currentl y available therapeutic modalities.