Directed effector cells selectively lyse human tumour cells

Abstract

Classical antibody-dependent cellular cytotoxicity (ADCC) involves effector cells that mediate damage of antibody-coated targets. Classical ADCC is probably responsible, at least in part, for in vivo allograft rejections, resistance to viral infections, parasite destruction and the rejection of tumours^1,2. Like complement^3,4, human effector cells mediate damage by creating a pore or channel in the target membrane, but the channel created by effector cells is 2.5 times larger (functional diameter ∼165Å) than the channel formed by complement^3,5. Classical ADCC is inhibited by low concentrations of immune complexes which compete with target-bound antibody for effector cell Fc receptors⁶. Because many clinically important diseases, such as certain cancers and systemic infections, have been shown to result in circulating antigen–antibody complexes, it seems likely that these immune complexes might inhibit the ADCC component of host defense mechanism in these diseases. A major advantage to the host might result from the attachment of antibody to effector cells first; either via the Fc receptor⁷, which is a weak interaction; by antibody ‘associating’ with effector cells⁸, which is very transient; or by binding antibody to the cellular membrane of effector cells⁹. Here I report the specificity of such antibody-directed ADCC effectors for antigen-bearing targets in vitro.