{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:36:09Z","timestamp":1793644569946,"version":"4.5.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Targeting tumor angiogenesis through vascular endothelial growth factor (VEGF) blockade represents a promising strategy for melanoma treatment. Here, we evaluate the therapeutic potential of HEBERSaVax, an anti-VEGF active immunotherapy, in aggressive B16-F10 syngeneic melanoma models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The antitumor activity of HEBERSaVax, formulated with aluminum phosphate adjuvant, was evaluated in C57BL\/6 mice using two distinct B16-F10 melanoma models (i): subcutaneous inoculation to assess primary tumor growth inhibition, and (ii) intravenous inoculation to quantify lung metastasis suppression. Tumor vasculature and microenvironment changes were analyzed via immunohistochemistry (CD31, \u03b1-SMA, CD4, CD8).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HEBERSaVax significantly reduced primary tumor volume and weight in subcutaneous implants compared to adjuvant controls. Histopathological analysis revealed potent angiogenesis inhibition, decreased CD31\n                      <jats:sup>+<\/jats:sup>\n                      vessel density, and vascular remodeling. Concomitant with tumor control, we observed changes in the tumor microenvironment, including a reduction in \u03b1-SMA\n                      <jats:sup>+<\/jats:sup>\n                      pericytes and an increase in the infiltration of CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. In the metastatic model, HEBERSaVax-treated mice showed fewer pulmonary nodules versus controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our results demonstrate that HEBERSaVax mediates dual antitumor efficacy by simultaneously suppressing VEGF-dependent angiogenesis and promoting immune-related changes in the melanoma microenvironment. These findings support the further development of HEBERSaVax as a promising active immunotherapy for VEGF-driven advanced melanoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1667651","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:17:32Z","timestamp":1766121452000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti-VEGF immunotherapy with HEBERSaVax suppresses melanoma growth and metastasis via angiogenesis blockade and enhanced T-cell 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