Potentiation by interleukin 2 of Burkitt's lymphoma therapy with anti-pan B (anti-CD19) monoclonal antibodies in a mouse xenotransplantation model

To study the immunotherapeutic potential of monoclonal antibodies (mAbs) directed against the human pan-B-cell antigen CD19, a xenotransplantation model was developed in which the human Burkitt's cell line Daudi is s.c. transplanted into nude mice. IgG1, IgG2b, and IgG2a isotype variants of the anti-CD19 mAb (CLB-CD19) were tested for their capacity to inhibit the growth of 10 x 10(6) Daudi cells injected s.c. into nude mice. When mAb treatment was started 30 min after the injection of tumor cells, only the IgG2a isotype of CLB-CD19 had a marked antitumor effect in vivo. If treatment with IgG2a anti-CD19 mAb alone was delayed until Day 10 after tumor injection, no therapeutic effect was observed. However, the combination of this delayed mAb treatment with recombinant interleukin 2 (rIL-2) inhibited the growth of the Daudi cells in the nude mice, while treatment with rIL-2 alone was ineffective. The results of in vitro experiments showed that peritoneal exudate cells were able to inhibit the proliferation of Daudi cells in the presence of the IgG2a isotype variant of CLB-CD19 mAb but not in the presence of the other CLB-CD19 mAb isotype variants. Fresh nude mouse spleen cells did not mediate antibody-dependent cellular cytotoxicity against CLB-CD19 mAb-sensitized Daudi cells, irrespective of the isotype used for sensitization. However, preculture of these spleen cells with rIL-2 induced antibody-dependent cellular cytotoxicity against CD19+ target cells sensitized with CLB-CD19 mAb of all isotypes. These results indicate that it is possible to enhance mAb-dependent effector systems in vivo with the lymphokine rIL-2