{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:30:30Z","timestamp":1786681830356,"version":"build-2736575974"},"reference-count":72,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["5.2.1.1.i.0\/2\/24\/I\/CFLA\/001"],"award-info":[{"award-number":["5.2.1.1.i.0\/2\/24\/I\/CFLA\/001"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"award":["5.2.1.1.i.0\/2\/24\/I\/CFLA\/001"],"award-info":[{"award-number":["5.2.1.1.i.0\/2\/24\/I\/CFLA\/001"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Plant-derived virus-like particles (VLPs) are emerging nanoplatforms for local cancer immunotherapy, yet their relative performance across structurally distinct particles remains insufficiently defined. Methods: We performed a comparative benchmarking study of eleven plant-derived VLPs spanning diverse architectures and functional properties using an integrated workflow of physicochemical characterization, immune-functional profiling, and in vivo evaluation. All VLPs were produced in endotoxin-minimized ClearColi BL21 (DE3), enabling assessment of intrinsic particle-associated immunostimulatory activity with reduced bacterial endotoxin confounding. Results: In vitro, several VLPs stimulated macrophage-associated responses and enhanced tumor cell killing, although classical M1\/M2 polarization markers in RAW264.7 cells did not consistently predict functional cytotoxicity. In a subset of candidates, HEK-TLR3 reporter activity varied substantially under RNA-normalized conditions and was not predicted solely by total RNA content or apparent RNA size distribution. Five candidates were advanced to intratumoral evaluation in the male-derived B16-F10 melanoma model, where CCMV-ss and CMVtt showed trends toward reduced tumor progression and increased immune cell infiltration in male mice. Furthermore, host sex-associated differences in baseline immune features were observed, though these must be interpreted with caution given the H-Y antigen-driven immunogenicity inherent to the male-derived B16-F10 model in female hosts. Conclusions: This study establishes a standardized comparative framework linking plant VLP properties with immune-functional performance and identifies CCMV-ss and CMVtt as promising candidates for further development as locally administered cancer immunotherapy nanoplatforms.<\/jats:p>","DOI":"10.3390\/vaccines14080697","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:45:06Z","timestamp":1786545906000},"page":"697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Evaluation of Plant-Derived Virus-like Particles as Intratumoral Immunotherapy Agents"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-0473","authenticated-orcid":false,"given":"Anete","family":"Ogrina-Komarova","sequence":"first","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9002-3131","authenticated-orcid":false,"given":"Zane","family":"Kalnina","sequence":"additional","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9898-3035","authenticated-orcid":false,"given":"Rebeka","family":"Racina","sequence":"additional","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilija","family":"Zeltina","sequence":"additional","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Petrovska","sequence":"additional","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Balke","sequence":"additional","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricija","family":"Zaremba","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Riga Stradins University, Dzirciema 16, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Resne","sequence":"additional","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-4392","authenticated-orcid":false,"given":"Juris","family":"Jansons","sequence":"additional","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andris","family":"Zeltins","sequence":"additional","affiliation":[{"name":"National Institute of Research and Innovation (NIRI), LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/s41423-020-0488-6","article-title":"The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications","volume":"17","author":"Zhang","year":"2020","journal-title":"Cell. 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