Co-administration of carcinoembryonic antigen and HIV TAT fusion protein with CpG-oligodeoxynucleotide induces potent antitumor immunity.
Although dendritic cells (DC) have been well demonstrated as a strong cellular adjuvant for a tumor vaccine, there are several limitations for clinical application. A protein-based vaccine using a potent adjuvant is an appealing approach for tumor antigen-specific immunotherapy because of their simplicity, safety, efficacy and capacity for repeated administration. CpG-oligodeoxynucleotides (ODN) have been used as adjuvants to stimulate innate and adaptive immune responses for cancer treatment. The authors evaluated the adjuvant effects of CpG-ODN in a vaccine incorporating recombinant fusion protein of the HIV TAT PTD domain and carcinoembryonic antigen (TAT-CEA). Mice vaccinated with TAT-CEA and CpG-ODN (TAT-CEA + CpG) showed enhanced CEA-specific immunity, including cytotoxic T-lymphocytes (CTL) activity and interferon (IFN)-gamma secreting T cells compared with CEA and CpG-ODN (CEA + CpG) or TAT-CEA vaccination alone. Vaccination with TAT-CEA + CpG elicited Th1-based responses, as indicated by the higher ratio of immunoglobulin (Ig)G2a antibody/IgG1 antibodies specific for CEA. The survival rate was significantly increased after vaccination with TAT-CEA + CpG in a tumor model using MC38/CEA2. Furthermore, the TAT-CEA +/- CpG vaccine groups showed similar antitumor immunity to the CEA peptide-pulsed DC (CEA peptide/DC) vaccine groups. These data suggest that coadministration of TAT fusion protein with CpG-ODN may serve as a potential formulation for enhancing antitumor activity.
Woo
Sun-Je
SJ
Department of Microbiology and Immunology, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seochu-Gu, Seoul 137-701, Korea.
Kim
Chang-Hyun
CH
Park
Mi-Young
MY
Kim
Hye-Sung
HS
Sohn
Hyun-Jung
HJ
Park
Jung-Sun
JS
Kim
Hyung-Jin
HJ
Oh
Seong-Taek
ST
Kim
Tai-Gyu
TG
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D051017:Apoptosis Regulatory Proteins; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; C512124:HIV-TAT-survivin (T34A) protein; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus