SPECIFIC TARGETING OF PHOTOTOXIC HAPTENATED LIPOSOMES TO A HAPTEN-SPECIFIC B-CELL LYMPHOMA

A method is reported to eliminate B lymphocytes specific for a haptena ted lipid by using the lipid hapten to target a photosensitive drug to them, The photosensitizer eosin was coupled to a phospholipid and inc orporated into trinitrophenol (TNP)-bearing small unilamellar vesicles of egg phosphatidylcholine (PC) and cholesterol in order to target th e photosensitizer to B lymphoma cells (A20-HL) with TNP-specific membr ane IgM receptors in vitro, Exposure of the treated cells to visible l ight led to an antigen-specific toxic effect indicated by inhibition o f cell proliferation. A significantly higher concentration of liposoma l eosin was required to inhibit control B cells, These were geneticall y identical B lymphoma cells (A20-2J) which lack only the DNA for the surface antigen receptor. Furthermore, pretreatment with TNP-conjugate d keyhole limpet hemocyanin or anti-IgM antibody abolished the antigen -specific toxic effect, confirming that the TNP-targeted liposomal eos in mediates its effect by binding to the Ig antigen receptors on TNP-s pecific B cells, Incubation of cells with the TNP-bearing phototoxic l iposomes at 4 degrees C instead of 37 degrees C did not alter the anti gen-specific targeting effect, suggesting that uptake of the liposomal drug into the cells is not necessary for its toxic effect, Replacemen t of the liposomal phospholipid (egg PC) with saturated species of PC having higher phase transition temperatures or with sphingo myelin cau sed a decrease of the antigen-specific effect, These results demonstra te the potential use of antigen-bearing liposomal phototoxic drugs for the purpose of targeting and eliminating B cells with antigen-specifi c surface Ig receptors. (C) 1996 Academic Press, Inc.