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 has been manufactured and approved for clinical use, is readily available, and can be easily used as an adjuvant. These characteristics prompted us to investigate the effectiveness of DOTAP as an adjuvant to induce immune responses and protective immunity in mice using baculovirus-derived carcinoembryonic antigen (bV-CEA) as a model antigen. Two routes 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 differences 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. The 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 higher in the s.c. immunized animals). No differences in immunological responses were seen using either 25 or 10 microg of bV-CEA three times. An amount of 25 microg of bV-CEA/DOTAP given by s.c. immunization was sufficient in protecting mice from the transplant of syngeneic tumor cells transduced with the human CEA gene. We conclude that the cationic liposome DOTAP may be a useful immunoadjuvant for active anti-tumor immunotherapy in future clinical trials. This study will help to define the most effective way to use such an adjuvant.
Bei
R
R
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Guptill
V
V
Masuelli
L
L
Kashmiri
S V
SV
Muraro
R
R
Frati
L
L
Schlom
J
J
Kantor
J
J
D000818:Animals; D000941:Antigens / Q000276:immunology*; D016367:Baculoviridae / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005229:Fatty Acids, Monounsaturated / Q000276:immunology*; D005456:Fluorescent Dyes; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000517:prevention & control; D000644:Quaternary Ammonium Compounds / Q000276:immunology*; D011994:Recombinant Proteins
D000941:Antigens; D002272:Carcinoembryonic Antigen; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane