ANTI-CD45 AND ANTI-CD52 (CAMPATH) MONOCLONAL-ANTIBODIES EFFECTIVELY ELIMINATE SYSTEMICALLY DISSEMINATED HUMAN NON-HODGKINS-LYMPHOMA B-CELLSIN SCID MICE

Severe combined immunodeficient (Scid) mice inoculated with the human t(14;18)-positive B cell lines DoHH2 and BEVA develop lethal systemica lly disseminated lymphoma (de Kroon et al., Leukemia 8:1385, and Blood 80 [supp] 1]:436). These models were used to study the therapeutic ef fect of rat-anti-human CD52 (Campath-1G) or CD45 monoclonal antibodies (mAbs) on systemically disseminated tumor cells and on tumor cells pr esent in solid tumor masses. Both mAbs were effective in inhibiting gr owth of systemically disseminated malignant cells. When treatment with anti-CD52 or anti-CD45 mAbs at a dose of 30 mu g/mouse/d for 4 days w as started 24 hours after intravenous inoculation of human DoHH2 or BE VA cells, a 3-log kill of tumor cells was observed as measured by prol onged survival. after treatment, surviving animals injected with high numbers of BEVA cells showed tumor masses in liver, kidney, and mesent eric lymph nodes. In contrast to nontreated animals, however, only low numbers of malignant cells were found in peripheral blood, and bone m arrow was free of tumor cells. Similarly, after mAb treatment of mice inoculated subcutaneously (sc) with DoHH2 cells, no tumor cells were f ound in the bone marrow, and few DoHH2 cells could be detected in the peripheral blood, spleen, liver, kidney, or lung. In contrast, tumor c ells present in subcutaneous tumors and axillary lymph nodes were rela tively unaffected by mAb therapy. The presence of rat immunoglobulin ( Ig) could be demonstrated on surviving tumor cells. The presence of mu rine macrophages in areas in these tumors that were depleted of DoHH2 cells suggested that the mAb-mediated antitumor effect observed in the Scid mouse model is mediated by cellular mechanisms. Apparently these mechanisms were not sufficient to eliminate the fast-growing tumor ce lls present in the protected sites. Our results indicate that treatmen t with anti-CD52 or anti-CD45 mAbs potentially may be useful as adjuva nt immunotherapy for systemically disseminated B cell lymphoma.