TY - JOUR
T1 - Targeting apoptotic tumor cells to FcγR provides efficient and versatile vaccination against tumors by dendritic cells
AU - Akiyama, Kenichi
AU - Ebihara, Shin
AU - Yada, Ayumi
AU - Matsumura, Kimio
AU - Aiba, Setsuya
AU - Nukiwa, Toshihiro
AU - Takai, Toshiyuki
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2003/2/15
Y1 - 2003/2/15
N2 - 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 (FcγRs) on DCs. It was found that when compared with ATCs, ATC-ICs were efficiently internalized by DCs via FcγRs, 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.
AB - 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 (FcγRs) on DCs. It was found that when compared with ATCs, ATC-ICs were efficiently internalized by DCs via FcγRs, 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.
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U2 - 10.4049/jimmunol.170.4.1641
DO - 10.4049/jimmunol.170.4.1641
M3 - Article
C2 - 12574326
AN - SCOPUS:0037442125
VL - 170
SP - 1641
EP - 1648
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -