The optimal interval for dendritic cell vaccination following adoptive T cell transfer is important for boosting potent anti-tumor immunity.
The gradual induction of immune responses by dendritic cell (DC) vaccination or the rapid decrease of adoptively transferred T cells may be major limitations in complete treatment of established tumors by active or passive immunization. The numbers of carcinoembryonic antigen (CEA)-specific T cells increased on 7th day and decreased from 2 weeks after repeated vaccination with CEA-peptide-pulsed DCs. Adoptively transferred CEA-specific T cells were detectable on day 1 and reached their peak by day 4, and thereafter decreased. On the basis of these results, a combined immunotherapy of DC vaccination following adoptive T cell transfer was performed to overcome these limitations of each modality. The injection of DCs within 1 day after adoptive T cell transfer showed a synergistic effect. However, when the DC vaccine was administered on day 3 or 7, CEA-specific T cells gradually declined. This concomitant immunization significantly inhibited the tumor growth than the DC vaccine administered on day 3 or 7 in 10 days tumor model. Moreover, the concomitant immunization showed potent anti-tumor effects resulting in complete inhibition of tumor growth in 2 days tumor model. These results suggest that the optimal interval for the DC vaccination following adoptive T cell transfer is important for boosting antigen-specific T cell responses and this combined immunotherapy may provide a potent therapeutic strategy for cancer treatment.
Park
Mi-Young
MY
Department of Microbiology and Immunology, Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, South Korea.
Kim
Chang-Hyun
CH
Sohn
Hyun-Jung
HJ
Oh
Seong-Taek
ST
Kim
Sung-Guh
SG
Kim
Tai-Gyu
TG
D019264:Adoptive Transfer; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007115:Immunization Schedule; D016219:Immunotherapy, Adoptive; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014018:Tissue Distribution
D002272:Carcinoembryonic Antigen