Cytotoxic liposomes: Membrane interleukin 1 presented in multilamellar vesicles

Paraformaldehyde-fixed lipopolysaccharide (LPS)-activated human monocytes produced significant lysis of the human melanoma cell line A375. The cytotoxic activity was retained following treatment of the fixed monocytes with antitumor necrosis factor (anti-TNF) antibodies but was specifically inhibited by a mixture of anti-TNF and anti-interleukin 1 (anti-IL 1) antibodies. A375 cells were also killed by plasma membranes purified from LPS-activated human blood monocytes. This activity was specifically inhibited by anti-IL 1α antibodies, but only partially inhibited by anti-IL 1β antibodies. CHAPS detergent-extracted plasma-membrane IL 1 in its soluble form or associated with lyophilized liposomes was also able to kill A375 cells, and this antitumor activity was inhibited by anti-IL 1 antibodies. These results suggest that membrane IL 1, primarily IL 1α, was cytotoxic for the A375 cells. CKS-17, a peptide synthesized with homology to a highly conserved region of the immunosuppressive retroviral envelope protein P15E, when covalently bound to BSA partially inhibited the IL 1 activities of tumor cell cytotoxicity and T-cell clone proliferation, displayed by purified plasma membranes, detergent-extracted membrane IL 1, or membrane IL 1 associated with liposomes. These findings indicate that cytotoxic membrane IL 1 can be solubilized by detergent, bound to the surface of liposomes, and specifically inhibited by anti-IL 1 antibodies or the immunosuppressive peptide CKS-17.