{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:00:32Z","timestamp":1781071232853,"version":"3.54.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The shift toward precision medicine in cancer immunotherapy has increased demand for rapid, scalable production platforms for personalized vaccine antigens targeting neoantigens and tumor-associated antigens. Escherichia coli-based recombinant protein production represents a globally established system offering speed and cost-effectiveness, yet the immunogenic potential of soluble antigens produced via this platform remains incompletely characterized. Here, we systematically evaluated the capacity of E. coli-derived soluble antigen formulations to elicit anti-tumor T cell responses. Using ClearColi BL21 (DE3), a lipopolysaccharide (LPS)-truncated strain free of endotoxic contamination, we produced soluble formulations containing murine OVA-derived epitopes.\n                    <jats:italic>In vitro<\/jats:italic>\n                    antigen presentation assays revealed minimal T cell activation despite high numbers of CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, indicating compromised antigen presentation capacity. However,\n                    <jats:italic>in vivo<\/jats:italic>\n                    adoptive transfer experiments demonstrated strongly inducible T cell expansion in draining and non-draining lymph nodes, with high frequencies of antigen-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells producing IFN-\u03b3 and TNF-\u03b1. Prime-boost vaccination strategies in experimental melanoma models achieved protective efficacy and durable survival with persistent antigen-specific T cell responses throughout the observation period. Under stringent single-prime conditions, transient T cell frequencies were observed without long-term tumor control.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1840895","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:20:15Z","timestamp":1781068815000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Soluble multi\u2212epitope protein vaccination leverages antigen availability to drive CD8+ T cell immunity and tumor control"],"prefix":"10.3389","volume":"17","author":[{"given":"Thomas M. E. V.","family":"van den Brekel","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam institute for Immunology and Infectious diseases, Amsterdam UMC, Location VUmc","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J. W.","family":"Goossens-Kruijssen","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam institute for Immunology and Infectious diseases, Amsterdam UMC, Location VUmc","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Olesek","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam institute for Immunology and Infectious diseases, Amsterdam UMC, Location VUmc","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Nardini","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam institute for Immunology and Infectious diseases, Amsterdam UMC, Location VUmc","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Koningstein","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"van Elk","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam institute for Immunology and Infectious diseases, Amsterdam UMC, Location VUmc","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter S. P.","family":"Jong","sequence":"additional","affiliation":[{"name":"Abera Bioscience AB","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"Duinkerken","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam institute for Immunology and Infectious diseases, Amsterdam UMC, Location VUmc","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Luirink","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit","place":["Amsterdam, Netherlands"]},{"name":"Abera Bioscience AB","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"van Kooyk","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam institute for Immunology and Infectious diseases, Amsterdam UMC, Location VUmc","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2396","article-title":"Recent advances in the molecular design of synthetic vaccines","volume":"7","author":"Jones","year":"2015","journal-title":"Nat Chem"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0022-1759(96)00066-x","article-title":"Recent advances in multiple antigen peptides","volume":"196","author":"Tam","year":"1996","journal-title":"J Immunol 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