A Novel Platform for Cancer Vaccines: Antigen-Selective Delivery to Splenic Marginal Zone B Cells via Repeated Injections of PEGylated Liposomes

Taro Shimizu, Amr Abu S. Lila, Yoshino Kawaguchi, Yuna Shimazaki, Yuki Watanabe, Yu Mima, Yosuke Hashimoto, Keiichiro Okuhira, Gert Storm, Yu Ishima, Tatsuhiro Ishida*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Treating cancer with vaccines has been a challenge. In this study, we introduce a novel Ag delivery platform for cancer vaccines that delivers an encapsulated Ag to splenic marginal zone B (MZ-B) cells via the aid of a PEGylated liposome (PL) system. Splenic MZ-B cells have recently attracted interest as alternative APCs. In mice, preimmunization with empty (no Ag encapsulation) PLs triggered the efficient delivery of a subsequent dose of Ag-containing PLs, injected 3 d later, to the spleen compared with a single dose of Ag-containing PLs. In addition, immunization with empty PLs allowed three subsequent sequential injections of OVA-PLs to efficiently induce α CTL response against OVA-expressing murine thymoma (EG7-OVA) cells and resulted in in vivo growth inhibition of subsequently inoculated EG7-OVA cells. However, these sequential treatments require repeated immunizations to achieve their antitumor effect. Therefore, to improve the antitumor effect of our novel vaccine system, an adjuvant, a-galactosylceramide (αGC), was incorporated into the OVA-PLs (αGC/OVA-PLs). As expected, the incorporation of aGC reduced the required number of immunizations with OVA-PLs to the point that a single immunization treatment with empty PLs and an injection of αGC/OVA-PL efficiently triggered a potent CTL induction, resulting in a rejection of the development and a suppression of the growth of tumors that had already developed s.c. Results of this study indicate that a novel Ag delivery platform that grants efficient Ag delivery to splenic MZ-B cells shows promise as a therapeutic modality for conquering tumor growth and/or progression. The Journal of Immunology, 2018, 201: 2969-2976.

Original languageEnglish
Pages (from-to)2969-2976
Number of pages8
JournalJournal of immunology
Volume201
Issue number10
DOIs
Publication statusPublished - 15 Nov 2018
Externally publishedYes

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