Vaccine Based on Dendritic Cells Electroporated with an Exogenous Ovalbumin Protein and Pulsed with Invariant Natural Killer T Cell Ligands Effectively Induces Antigen-Specific Antitumor Immunity

Akihiro Watanabe; Kimihiro Yamashita; Mitsugu Fujita; Akira Arimoto; Masayasu Nishi; Shiki Takamura; Masafumi Saito; Kota Yamada; Kyosuke Agawa; Tomosuke Mukoyama; Masayuki Ando; Shingo Kanaji; Takeru Matsuda; Taro Oshikiri; Yoshihiro Kakeji

doi:10.3390/cancers14010171

Vaccine Based on Dendritic Cells Electroporated with an Exogenous Ovalbumin Protein and Pulsed with Invariant Natural Killer T Cell Ligands Effectively Induces Antigen-Specific Antitumor Immunity

Cancers (Basel). 2021 Dec 30;14(1):171. doi: 10.3390/cancers14010171.

Authors

Affiliations

¹ Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
² Center for Medical Education and Clinical Training, Kindai University Faculty of Medicine, 377-2 Onohigashi, Osaka 589-0014, Japan.
³ Division of Gastrointestinal Surgery, Saiseikai Suita Hospital, Kawazono-cho, Suita 564-0013, Japan.
⁴ Division of Gastrointestinal Surgery, Konan Medical Center, Kamokogahara, Higashinada, Kobe 658-0064, Japan.
⁵ Department of Immunology, Kindai University Faculty of Medicine, 377-2 Ono-higashi, Osakasayama 589-0014, Japan.
⁶ Department of Disaster and Emergency and Critical Care Medicine, Graduate School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

Abstract

(1) Background: Cancer vaccines are administered to induce cytotoxic CD8⁺ T cells (CTLs) specific for tumor antigens. Invariant natural killer T (iNKT) cells, the specific T cells activated by α-galactosylceramide (α-GalCer), play important roles in this process as they are involved in both innate and adaptive immunity. We developed a new cancer vaccine strategy in which dendritic cells (DCs) were loaded with an exogenous ovalbumin (OVA) protein by electroporation (EP) and pulsed with α-GalCer. (2) Methods: We generated bone marrow-derived DCs from C57BL/6 mice, loaded full-length ovalbumin proteins to the DCs by EP, and pulsed them with α-GalCer (OVA-EP-galDCs). The OVA-EP-galDCs were intravenously administered to C57BL/6 mice as a vaccine. We then investigated subsequent immune responses, such as the induction of iNKT cells, NK cells, intrinsic DCs, and OVA-specific CD8⁺ T cells, including tissue-resident memory T (T_RM) cells. (3) Results: The OVA-EP-galDC vaccine efficiently rejected subcutaneous tumors in a manner primarily dependent on CD8⁺ T cells. In addition to the OVA-specific CD8⁺ T cells both in early and late phases, we observed the induction of antigen-specific T_RM cells in the skin. (4) Conclusions: The OVA-EP-galDC vaccine efficiently induced antigen-specific antitumor immunity, which was sustained over time, as shown by the T_RM cells.

Keywords: antitumor immunity; dendritic cells; electroporation; iNKT cell-enhanced vaccine; tissue-resident memory T cells.