{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:16:48Z","timestamp":1791494208779,"version":"4.3.4"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T00:00:00Z","timestamp":1409616000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T00:00:00Z","timestamp":1409616000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T00:00:00Z","timestamp":1409616000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Because existing therapeutic cancer vaccines provide only a limited clinical benefit, a different vaccination strategy is necessary to improve vaccine efficacy. We developed a nanoparticulate cancer vaccine by encapsulating a synthetic long peptide antigen within an immunologically inert nanoparticulate hydrogel (nanogel) of cholesteryl pullulan (CHP). After subcutaneous injection to mice, the nanogel-based vaccine was efficiently transported to the draining lymph node, and was preferentially engulfed by medullary macrophages but was not sensed by other macrophages and dendritic cells (so-called \u201cimmunologically stealth mode\u201d). Although the function of medullary macrophages in T cell immunity has been unexplored so far, these macrophages effectively cross-primed the vaccine-specific CD8+ T cells in the presence of a Toll-like receptor (TLR) agonist as an adjuvant. The nanogel-based vaccine significantly inhibited in vivo tumor growth in the prophylactic and therapeutic settings, compared to another vaccine formulation using a conventional delivery system, incomplete Freund\u2019s adjuvant. We also revealed that lymph node macrophages were highly responsive to TLR stimulation, which may underlie the potency of the macrophage-oriented, nanogel-based vaccine. These results indicate that targeting medullary macrophages using the immunologically stealth nanoparticulate delivery system is an effective vaccine strategy.<\/jats:p>","DOI":"10.1021\/nn502975r","type":"journal-article","created":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T13:30:35Z","timestamp":1409664635000},"page":"9209-9218","source":"Crossref","is-referenced-by-count":140,"title":["Nanogel-Based Immunologically Stealth Vaccine Targets Macrophages in the Medulla of Lymph Node and Induces Potent Antitumor Immunity"],"prefix":"10.1021","volume":"8","author":[{"given":"Daisuke","family":"Muraoka","sequence":"first","affiliation":[{"name":"Mie University Graduate School of Medicine , , ,","place":["Mie, Japan, 514-8507"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naozumi","family":"Harada","sequence":"additional","affiliation":[{"name":"Mie University Graduate School of Medicine , , ,","place":["Mie, Japan, 514-8507"]},{"name":"ImmunoFrontier, Inc. , , ,","place":["Tokyo, Japan, 101-0021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Mie University Graduate School of Medicine , , ,","place":["Mie, Japan, 514-8507"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiro","family":"Tahara","sequence":"additional","affiliation":[{"name":"Kyoto University Graduate School of Engineering , , ,","place":["Kyoto, Japan, 615-8510"]},{"name":"Japan Science and Technology Agency (JST) , , ,","place":["Tokyo, Japan, 102-0076"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiyasu","family":"Momose","sequence":"additional","affiliation":[{"name":"Mie University Graduate School of Medicine , , ,","place":["Mie, Japan, 514-8507"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Sawada","sequence":"additional","affiliation":[{"name":"Kyoto University Graduate School of Engineering , , ,","place":["Kyoto, Japan, 615-8510"]},{"name":"Japan Science and Technology Agency (JST) , , ,","place":["Tokyo, Japan, 102-0076"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sada-atsu","family":"Mukai","sequence":"additional","affiliation":[{"name":"Kyoto University Graduate School of Engineering , , ,","place":["Kyoto, Japan, 615-8510"]},{"name":"Japan Science and Technology Agency (JST) , , ,","place":["Tokyo, Japan, 102-0076"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunari","family":"Akiyoshi","sequence":"additional","affiliation":[{"name":"Kyoto University Graduate School of Engineering , , ,","place":["Kyoto, Japan, 615-8510"]},{"name":"Japan Science and Technology Agency (JST) , , ,","place":["Tokyo, Japan, 102-0076"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Shiku","sequence":"additional","affiliation":[{"name":"Mie University Graduate School of Medicine , , ,","place":["Mie, Japan, 514-8507"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,9,2]]},"reference":[{"key":"2026082008305301200_cit1","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/nbt1332","article-title":"Exploiting Lymphatic Transport and Complement Activation in Nanoparticle Vaccines","volume":"25","author":"Reddy","year":"2007","journal-title":"Nat. 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