**3. Mode of action of APL**

Anti-cancer mechanisms of alkylphospholipids have been described and extensively discussed in some recent reviews (Danker et al., 2010; Gajate & Mollinedo, 2002; Gills & Dennis, 2009; van Blitterswijk & Verheij, 2008). Early interest focussed on immune stimulating activity of alkylphospholipids. It could be demonstrated that Miltefosine and other lipids of this class are able to activate T-cells and macrophages to express and release chemokines like GM-CSF (Vehmeyer et al., 1992), IFgamma (Hochhuth et al., 1992) and/or nitric oxide (NO) (Zeisig et al., 1995). This effect could be improved if the alkylphospholipids were used in liposomal form. Because of their amphiphilic structure, alkylphospholipids are able to form lamellar bilayers, if combined with lipids of opposite molecular shape. Liposomes were taken up by macrophages much better than the free, micellar lipids and induced, after cellular uptake, the release of IF gamma and NO (Eue et al., 1995). But their potency as immune stimulator was limited and not sufficient enough amount of chemokines was released for a complete inhibition of tumor cell proliferation.
