Modification of CEA with both CRT and TAT PTD induces potent anti-tumor immune responses in RNA-pulsed DC vaccination.
Carcinoembryonic antigen (CEA) is expressed on human colon carcinomas, is well characterized, and continues to be a promising target for cancer immunotherapy in humans. To enhance the immunogenecity of CEA, we developed a fusion gene (CRT-TAT-DeltaCEA) of the TAT protein transduction domain (PTD) and calreticulin (CRT) with human CEA devoid of its signal sequences (DeltaCEA) and evaluated anti-tumor immunity using RNA-pulsed dendritic cell (DC) vaccination. Mice vaccinated with DC by electroporation with mRNA encoding TAT-DeltaCEA (DC/TAT-DeltaCEA) and CRT-DeltaCEA (DC/CRT-DeltaCEA) had enhanced induction of tumor-specific cytotoxic T lymphocyte (CTL) and increased numbers of IFN-gamma-secreting T cells by ELISPOT, as compared to mice vaccinated with DC/DeltaCEA. DC/CRT-DeltaCEA and DC/TAT-DeltaCEA vaccines preferentially stimulated CD4+ and CD8+ T cells, respectively. The DC vaccine by electroporation with mRNA encoding CRT-TAT-DeltaCEA (DC/CRT-TAT-DeltaCEA) enhanced both CD4+ and CD8+ T cells. DC/CRT-TAT-DeltaCEA had the additional effects of CRT and TAT PTD and enhanced the anti-tumor effect against CEA-expressing tumors compared to DC/CRT-DeltaCEA or DC/TAT-DeltaCEA. These findings suggest that modification of CEA with both CRT and TAT PTD induces potent anti-tumor immune responses in RNA-pulsed DC vaccination and may be a useful approach for DC-based immunotherapy.
Kim
Sung-Guh
SG
Department of Microbiology and Immunology, Kang-Nam St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, Republic of Korea.
Park
Mi-Young
MY
Kim
Chang-Hyun
CH
Sohn
Hyun-Jung
HJ
Kim
Hye-Sung
HS
Park
Jung-Sun
JS
Kim
Hyung-Jin
HJ
Oh
Seong-Taek
ST
Kim
Tai-Gyu
TG
D000230:Adenocarcinoma / Q000276:immunology* / Q000628:therapy; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D037282:Calreticulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D018274:Electroporation; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
D037282:Calreticulin; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015696:Gene Products, tat; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins