Abstract
Monoclonal antibodies against human α-fetoprotein (AFP) or carcinoembryonic antigen (CEA) were conjugated to liposomes containing adriamycin (ADM), and their therapeutic effects were experimentally studied in vivo on AFP or CEA positive human solid tumors maintained in BALB/c nu/nu mice. The anti-tumor effect of antibody-conjugated liposomes containing ADM was immunologically specific and was greater than that of unconjugated liposomes containing ADM or that of ADM alone. Furthermore, tissue distribution studies revealed the selective delivery of ADM to tumors occurred with immunoliposomes. However, it was also revealed the liposomes are preferentially accumulated to the reticuloendothelial cells. To improve the therapeutic effects, we further prepared the following three types of liposomes and their therapeutic activities were assessed. (1) Fab′ fragment was introduced instead of whole molecule of antibody. These liposomes are expected to keep the antigen-binding activity of antibody intact. Actually, the therapeutic effect of liposomes with Fab′ fragment was greater than that of liposomes with whole molecule. (2) GMI gangliosides were incorporated into liposomes and with these liposomes the accumulation of ADM to reticuloendothelial cells was reduced. (3) Temperature-sensitive liposomes were prepared with dipalmitoylphosphatidylcholine. Combination of temperature sensitivity and monoclonal antibodies for targeting therapy is now in progress.
