Targeting apoptotic tumor cells to Fc gamma R provides efficient and versatile vaccination against tumors by dendritic cells.
Dendritic cells (DCs) loaded with tumor-associated Ags (TAAs) act as potent adjuvant that initiates antitumor immune responses in vivo. However, TAA-based DC vaccination requires prior identification of TAAs. Apoptotic tumor cells (ATCs) can be an excellent source for DC loading because their potential uncharacterized Ags would be efficiently presented to T cells without any prior characterization and isolation of these Ags. However, ATCs alone are considered to be inefficient for activating antitumor immunity, possibly because of their inability to induce DC maturation. In this study, the aim was to enhance antitumor immune response by taking advantage of ATCs that have been opsonized with IgG (ATC-immune complexes, ATC-ICs) so as to target them to FcR for IgG (FcgammaRs) on DCs. It was found that when compared with ATCs, ATC-ICs were efficiently internalized by DCs via FcgammaRs, and this process induced maturation of DCs, which was more efficient than that of ATCs. Importantly, ATC-IC loading was shown to be more efficient than ATCs alone in its capacity for inducing antitumor immunity in vivo, in terms of cytotoxic T cell induction and tumor rejection. These results show that using ATC-ICs may overcome the limitations and may enhance the immune response of current ATC-based DC vaccination therapy.
Akiyama
Kenichi
K
Department of Experimental Immunology and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Sendai, Japan.
Ebihara
Shin
S
Yada
Ayumi
A
Matsumura
Kimio
K
Aiba
Setsuya
S
Nukiwa
Toshihiro
T
Takai
Toshiyuki
T
D000818:Animals; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013945:Thymoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D014407:Tumor Cells, Cultured
D000936:Antigen-Antibody Complex; D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II; D017452:Receptors, IgG; D010047:Ovalbumin