title: Efficient induction of anti-tumor immunity by a TAT-CEA fusion protein vaccine with poly(I:C) in a murine colorectal tumor model.
abstract: Protein vaccines may be a useful strategy for cancer immunotherapy because recombinant tumor antigen proteins can be produced on a large scale at relatively low cost and have been shown to be safe for clinical application. However, protein vaccines have historically exhibited poor immunogenicity; thus, an improved strategy is needed for successful induction of immune responses. TAT peptide is a protein transduction domain composed of an 11-amino acid peptide (TAT(47-57): YGRKKRRQRRR). The positive charge of this peptide allows protein antigen fused with it to improve cell penetration. Poly(I:C) is a synthetic double-stranded RNA that is negatively charged and favors interaction with the cationic TAT peptide. Poly(I:C) has been reported on adjuvant role in tumor vaccine through promotion of immune responses. Therefore, we demonstrated that vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) can induce anti-tumor immunity in a murine colorectal tumor model. Splenocytes from mice vaccinated with a mixture of TAT-CEA fusion protein and poly(I:C) effectively induced CEA-specific IFN-γ-producing T cells and showed cytotoxic activity specific for MC-38-cea2 tumor cells expressing CEA. Vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) delayed tumor growth in MC-38-cea-2 tumor-bearing mice. Depletion of CD8(+) T cells and NK cells reversed the inhibition of tumor growth in an MC-38-cea2-bearing mice, indicating that CD8(+) T cells and NK cells are responsible for anti-tumor immunity by vaccine with a mixture of TAT-CEA fusion protein and poly(I:C). Taken together, these results suggest that poly(I:C) could be used as a potent adjuvant to induce the anti-tumor immunity of a TAT-CEA fusion protein vaccine in a murine colorectal tumor model.
authors.affiliation: College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Hye-Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Park
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D047589:Leukocyte Reduction Procedures; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics; D011070:Poly I-C / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; C497137:tat peptide (47-57), Human immunodeficiency virus 1; D007371:Interferon-gamma; D011070:Poly I-C