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抗 VEGF 免疫治疗联合 HEBERSaVax 通过阻断血管生成和增强 T 细胞浸润抑制黑色素瘤生长和转移

英文原题:Anti-VEGF immunotherapy with HEBERSaVax suppresses melanoma growth and metastasis via angiogenesis blockade and enhanced T-cell infiltration.

查看英文原题

Anti-VEGF immunotherapy with HEBERSaVax suppresses melanoma growth and metastasis via angiogenesis blockade and enhanced T-cell infiltration.

PubMed 2025/12/19(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

我们的结果表明,HEBERSaVax 通过同时抑制 VEGF 依赖性血管生成并促进黑色素瘤微环境中的免疫相关变化,介导了双重抗肿瘤疗效。这些发现支持进一步开发 HEBERSaVax 作为一种有前景的针对 VEGF 驱动的晚期黑色素瘤的主动免疫治疗。

研究思路结论见上方概要

通过血管内皮生长因子(VEGF)阻断靶向肿瘤血管生成是黑色素瘤治疗的一种有前景的策略。在此,我们评估了HEBERSaVax——一种抗VEGF主动免疫疗法——在侵袭性B16-F10同系黑色素瘤模型中的治疗潜力。

评估了以磷酸铝佐剂配制的 HEBERSaVax 在 C57BL/6 小鼠中的抗肿瘤活性,采用两种不同的 B16-F10 黑色素瘤模型:(i) 皮下接种以评估原发肿瘤生长抑制,(ii) 静脉接种以量化肺转移抑制。通过免疫组化(CD31、α-SMA、CD4、CD8)分析肿瘤血管和微环境变化。

与佐剂对照组相比,HEBERSaVax显著降低了皮下植入瘤的原发肿瘤体积和重量。组织病理学分析显示其具有强效的血管生成抑制作用,CD31+血管密度降低,并出现血管重塑。在肿瘤控制的同时,我们观察到肿瘤微环境的变化,包括α-SMA+周细胞减少以及CD4+和CD8+ T细胞浸润增加。在转移模型中,HEBERSaVax治疗组小鼠较对照组表现出更少的肺部结节。

展开英文摘要原文

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, α-SMA, CD4, CD8).

HEBERSaVax significantly reduced primary tumor volume and weight in subcutaneous implants compared to adjuvant controls. Histopathological analysis revealed potent angiogenesis inhibition, decreased CD31 + vessel density, and vascular remodeling. Concomitant with tumor control, we observed changes in the tumor microenvironment, including a reduction in α-SMA + pericytes and an increase in the infiltration of CD4 + and CD8 + T cells. In the metastatic model, HEBERSaVax-treated mice showed fewer pulmonary nodules versus controls. DISCUSSION: 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.

论文信息

作者
Morera-Díaz Y、García-Sanmartín J、Canaán-Haden C、Bequet-Romero M、Gonzalez-Moya I、Ayala-Ávila M、Tadic S、Garrido P
第一作者单位
Cancer Immunotherapy Group, Direction of Biomedical Research, Center for Genetic Engineering and Biotechnology (CIGB), BioCubaFarma, Havana, Cuba.Cuba
通讯作者单位
Angiogenesis Unit, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.Spain
期刊
Frontiers in immunology2025
原文标识
PubMed 41488668 · DOI 10.3389/fimmu.2025.1667651