This role of monocytes and natural killer cells in mediating antibody-dependent lysis of colorectal tumour cells

Monocytes and natural killer (NK) cells are known to be important effector cell populations in mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Purified monocyte and NK effector cell populations, from normal an d colorectal cancer (CRC) patients,,together with a number of murine (17-1A and 323/A3) and their chimaeric (c17-1A) or humanised (3622W94) equivalent s, and chimaeric (c) SF25 were compared for their ability to mediate ADCC o f colorectal tumour cells. The chimaeric and humanised antibodies were sign ificantly better at mediating tumour lysis than their murine equivalents wi th all-effector populations. When effector cells from CRC patients were use d the cSF25 antibody was significantly better than 3422W94 (P < 0.02) which , in turn, was significantly better than c17-1A (P < 0.03). Depletion of NK cells produced: a decrease in specific tumour lysis with all antibodies. I n addition a higher rate of NK cell death was observed in CRC patients duri ng the assay than in normal controls. The chimaeric and humanised antibodie s stained a similar percentage of the HT-29 target cells (>80%), but 3622W9 4 bound to significantly more cells from primary tumour biopsies than cSF-2 5 (P = 0.001). Together, the results suggest that NK cells are the most imp ortant effector cell type mediating ADCC in vitro, that there is some impai rment of NK function in CRC patients, and that cSF25 is the most potent ant ibody. For use in vivo the anti-Ep-CAM antibody 3622W94 would appear to be the most suitable reagent for further study.