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

## TL;DR

This study shows that HEBERSaVax, an anti-VEGF immunotherapy, reduces melanoma growth and spread by blocking blood vessel formation and boosting T-cell activity in mice.

## Contribution

The novel contribution is demonstrating HEBERSaVax's dual mechanism of angiogenesis blockade and immune enhancement in melanoma models.

## Key findings

- HEBERSaVax significantly reduced primary tumor volume and weight in subcutaneous melanoma models.
- Treatment led to decreased CD31+ vessel density and increased CD4+/CD8+ T-cell infiltration.
- Metastatic lung nodules were reduced in HEBERSaVax-treated mice compared to controls.

## Abstract

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.

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.

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.