Autologous human macrophages and anti-tumour cell therapy

Abstract

Most technical problems concerning the production of human macrophages have been resolved by cultures in hydrophobic plastic, gas-permeable bags. This process enables collection of non-adherent macrophages and is well adapted to the safety requirements of cell therapy. Under optimized culture conditions, about one billion macrophages are currently obtained from a single leukapheresis product. In most clinical trials, macrophages have been activated by interferon-gamma (IFNgamma). The injections have little or no toxic effect. The anti-tumour activity of the intravenous (i.v.) administrations is more pronounced in certain protocols than in others. The mechanism remains poorly understood. In vitro, the cytolytic effect of macrophages requires cell-to-cell contact but macrophages injected i.v. show no particular tropism for tumour tissue. This could result from modifications in adhesion molecules occurring during monocyte-macrophage differentiation which might modify recruitment in inflammatory foci. Macrophages can, however, infiltrate tumour cell clusters, which could explain their improved efficacy when injected intratumorally (i.t.). Moreover, several arguments would favour the use of macrophages as human tumour antigen-presenting cells (APCs). In vitro, macrophages are as efficient as monocyte-derived dendritic cells (MDDCs) in stimulating cytotoxic T lymphocyte (CTL) clones or circulating CTL precursors.