Cell membrane lipids as experimental therapeutic targets

Cell membranes contain numerous species of glycosphingolipids (GSL) and glycerophospholipids. Changes in the surface expression of these moieties that accompany malignant transformation are potential targets for immune therapies. There is increasing evidence that tumour specificity resides in the carbohydrate composition and topography of gangliosides and in the asymmetric distribution of phospholipids in the bilayer membrane. However, since these epitopes are not antigenic, circumvention of immunological tolerance to these self antigens is required to generate an effective immune response. New methodologies accomplish this by coupling these hapten-like lipid epitopes to immunogenic protein carriers. Indeed, the generation of immune responses to endogenous lipid antigens occurs in several autoimmune syndromes and may serve as natural models for therapeutic immune intervention that influence pathways critical to tumour angiogenesis, proliferation and apoptosis.