THE USE OF A CATIONIC LIPOSOME FORMULATION (DOTAP) MIXED WITH A RECOMBINANT TUMOR-ASSOCIATED ANTIGEN TO INDUCE IMMUNE-RESPONSES AND PROTECTIVE IMMUNITY IN MICE

The cationic liposome DOTAP is a well-known transfection reagent. It h as been manufactured and approved for clinical use, is readily availab le, and can be easily used as an adjuvant. These characteristics promp ted us to investigate the effectiveness of DOTAP as an adjuvant to ind uce immune responses and protective immunity in mice using baculovirus -derived carcinoembryonic antigen (bV-CEA) as a model antigen. Two rou tes of administration and a dose-response study of bV-CEA were used in BALB/c mice to define the magnitude of the immune response as well as the most effective route of immunization. The results demonstrate dif ferences in antibody titers, immunoglobulin (Ig)G isotype, and T-cell responses between the intravenous (i.v.) or subcutaneous (s.c.) route of immunization. The titer of the anti-CEA antibodies induced by the s .c. immunization was greater than the response by i.v. immunization. T he s.c. route enhanced the IgG2a/2b isotype, whereas i.v. immunization elicited primarily IgG1. T-cell proliferation responses and cytokine production paralleled the humoral response (i.e., production was highe r in the s.c. immunized animals). No differences in immunological resp onses were seen using either 25 or 10 mu g of bV-CEA three times. An a mount of 25 mu g of bV-CEA/DOTAP given by s.c. immunization was suffic ient in protecting mice from the transplant of syngeneic tumor cells t ransduced with the human CEA gene. We conclude that the cationic lipos ome DOTAP may be a useful immunoadjuvant for active anti-tumor immunot herapy in future clinical trials. This study will help to define the m ost effective way to use such an adjuvant.