Fas-deficient fully allogeneic dendritic cells administered via an intratumoral injection route show efficient antitumor effects in murine models.

Shinji Okano, Haruhiko Kondoh, Takeo Toshima, Hidekazu Nakagawara, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Mamoru Harada, Yasunobu Yoshikai, Yoshihiko Maehara

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Abstract

Dendritic cell (DC)-based immunotherapy is a potent, active and specific cancer immunotherapy, as DCs are preferable professional APCs (pAPCs) that prime the tumor-associated antigen (TAA) -specific CD8+ T-cell response. In DC-based immunotherapy, allogeneic DCs may be an alternative source of DCs for patients in whom it is difficult to obtain a sufficient number of quality-guaranteed, autologous DCs. However, the usefulness of fully allogeneic DCs in DC-based immunotherapy is controversial, and many investigators have failed to demonstrate that fully allogeneic DCs can induce an efficient antitumor effect in various experimental settings. In this study, we found that the injection of Fas-deficient fully allogeneic DCs via an intratumoral injection route exerted efficient antitumor effects, as did syngeneic DCs, but wild-type fully allogeneic DCs did not. Intratumoral injection therapy using Fas-deficient syngeneic DCs does not show superior tumor growth suppression compared to that using wild-type syngeneic DCs, suggesting that the inhibition of functional Fas may be critical for overcoming the unfavorable factor related to allogeneic DCs, especially overcoming the rejection response to alloantigens, in therapy using fully allogeneic DCs. In addition, the intratumoral injection therapy using Fas-deficient fully allogeneic DCs induced the generation of a significant tumor-specific CD8+ T-cell response, which is restricted by a host-derived major histocompatibility antigen. Therefore, intratumoral injection therapy using fully allogeneic DCs of which functional Fas is inhibited may be an alternative in clinical DC-based immunotherapy, under circumstances that do not allow the use of autologous DCs.

Original languageEnglish
Pages (from-to)15-26
Number of pages12
JournalUnknown Journal
Volume104
Issue number1
Publication statusPublished - Jan 2013

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Okano, S., Kondoh, H., Toshima, T., Nakagawara, H., Yoshizumi, T., Soejima, Y., Shirabe, K., Harada, M., Yoshikai, Y., & Maehara, Y. (2013). Fas-deficient fully allogeneic dendritic cells administered via an intratumoral injection route show efficient antitumor effects in murine models. Unknown Journal, 104(1), 15-26.