Murine neuroblastoma cured in vivo by an antibody-dependent cellular cytotoxicity reaction

CYTOLYSIS of antibody-coated tumour cells mediated by reticuloendothelial (RE) or bone marrow cells is a phenomenon of unknown biological relevance 1–4 . The specificity of the reaction lies in the antibody 5,6 ; probably most or all cells able to recognise the Fc fragment of the antibody molecule can mediate this reaction, including lymphocytes and monocytes 6,7 , circulating cultured transformed lymphoblasts 8 , polymorphonuclear leukocytes 9 and malignant reticulum cells 10 . In tumour systems the contribution of this reaction is difficult to distinguish in vivo from other cytolytic phenomena, including complement-dependent antibody-mediated cytotoxicity, T-cell cytotoxicity or cell killing exerted by “armed” macrophages 11,12 , all of which may be active in various degrees in different experimental circumstances. But antibody-dependent cellular cytotoxicity (ADCC), as this phenomenon has been termed 13 , seems to be of potential therapeutic interest because both its magnitude and specificity depend on specific antibody levels, and antibody levels may be potentially more manipulable in man than are the cellular elements of a host anti-tumour response. In addition, there is preliminary evidence that fixed tissue macrophages may be active in eliminating circulating metastatic cells by this mechanism 14 . It was therefore interesting to determine whether functional ADCC could be demonstrated in vivo independent of other cytolytic mechanisms since its demonstration has so far been limited to in vitro assays.