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

• Published in: The Journal of immunology (1950) 2018-11, Vol.201 (10), p.2969-2976
• Main Authors: Shimizu, Taro, Abu Lila, Amr S, Kawaguchi, Yoshino, Shimazaki, Yuna, Watanabe, Yuki, Mima, Yu, Hashimoto, Yosuke, Okuhira, Keiichiro, Storm, Gert, Ishima, Yu, Ishida, Tatsuhiro
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1701351

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 a 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, α-galactosylceramide (αGC), was incorporated into the OVA-PLs (αGC/OVA-PLs). As expected, the incorporation of αGC 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.