CYTOTOXICITY OF WHITE BLOOD-CELLS ACTIVATED BY GRANULOCYTE-COLONY-STIMULATING FACTOR, GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR AND MACROPHAGE-COLONY-STIMULATING FACTOR AGAINST TUMOR-CELLS IN THE PRESENCE OF VARIOUS MONOCLONAL-ANTIBODIES/

Unconjugated monoclonal antibodies (mAb) kill tumor cells in vivo by a ctivating immune functions. One of these is ADCC (antibody-dependent c ellular cytotoxicity). The efficacy of mAbs might be augmented if the cytotoxic capacity of the effector cells could be increased. In this s tudy the augmenting effect of granulocyte-colony-stimulating factor (G -CSF), granulocyte/macrophage(GM)-CSF and macrophage(M)-CSF was analyz ed. Effector cells [peripheral blood mononuclear cells (PBMC) or granu locytes] were activated for 4-6 h by the respective CSF and assayed in an 18-h Cr-51-release assay. Human colorectal, lymphoma, glioma and m elanoma cell Lines were target cells. Mouse mAbs of different isotypes , as well as chimeric and humanized mAbs, were used. mAbs having the h uman Fc part of the IgG molecule were the most effective. The killing capacity of PBMC as well as of granulocytes was statistically signific antly enhanced when mAbs were added. M-CSF and GM-CSF were the best CS F for augmenting the lyric capacity of PBMC in ADCC. G-CSF had no sign ificant effect on PBMC. Spontaneous cytolysis of PBMC was significantl y augmented only by M-CSF. Granulocytes were, in general, significantl y less effective than PBMC but may be equally effective killer cells t ogether with mouse or human mAbs of the IgG1 isotype, particularly aga inst melanoma cells. Granulocytes may also be significantly stimulated to increased lytic capacity when activated with G-CSF or GM-CSF. On t he basis of the present evaluation, clinical trials in tumor patients are warranted, combining mAbs with GM-CSF or M-CSF. Preference might b e given to GM-CSF as this cytokine activates both PBMC and granulocyte s.