What question did this study set out to answer?

To evaluate the efficacy of an mRNA vaccine targeting adrenomedullin in inhibiting tumor growth and angiogenesis in melanoma models.

April 5, 2026

Abstract 4783: An mRNA vaccine targeting angiogenesis elicits a robust immune response and inhibits tumor growth and angiogenesis in two mouse melanoma models

Key Points

To evaluate the efficacy of an mRNA vaccine targeting adrenomedullin in inhibiting tumor growth and angiogenesis in melanoma models.
Developed an mRNA vaccine encoding keyhole limpet hemocyanin peptide linked to adrenomedullin
Administered the vaccine encapsulated in lipid nanoparticles to C57BL/6 mice
Assessed vaccine effects in lung metastasis and subcutaneous melanoma models after multiple immunizations
Analyzed blood and organs for immune responses and tumor characteristics post-vaccination
Vaccinated mice showed higher anti-adrenomedullin IgG levels and increased CD8+ T cell counts compared to controls
Significant reduction in lung metastases number and size and decreased tumor-associated blood vessels in the lung model
In the subcutaneous model, vaccination delayed tumor initiation and reduced tumor volume and angiogenesis
No systemic toxicity or significant weight changes were observed

Abstract

Abstract Background: Angiogenesis is essential for tumor growth, metastasis, and the establishment of an immunosuppressive microenvironment. By supporting nutrient delivery and modulating immune cell infiltration, tumor-driven angiogenesis promotes both malignant progression and immune evasion. Among its key regulators, adrenomedullin (AM) is a potent pro-angiogenic factor frequently overexpressed in solid tumors. To explore its therapeutic potential, we developed an mRNA vaccine encoding a fusion antigen composed of a small keyhole limpet hemocyanin (KLH) peptide, as a hapten, linked to mouse AM. Methods: The in vitro transcribed mRNA was encapsulated in lipid nanoparticles (LNPs) and administered to C57BL/6 mice, with empty LNPs serving as controls. The vaccine was evaluated in two distinct melanoma models: an experimental lung metastasis model induced by intravenous injection of B16-F10 melanoma cells, and a subcutaneous melanoma model. After four immunizations, melanoma cells were injected, followed by a fifth immunization. Mice were sacrificed once tumors reached humane endpoints and blood and organs were analyzed. Results: Vaccinated mice exhibited significant increases in anti-AM IgG titers (p= 0.040) and CD8+ T cell numbers (p=0.033) compared to controls. In the lung metastasis model, immunization resulted in a significant reduction in both the number (p=0.028) and size of lung metastases (p=0.020) as well as a decrease in the number of tumor-associated blood vessels (p=0.046), without disrupting normal vasculature as assessed in SMAA-GFP transgenic mice. In the subcutaneous model, vaccination delayed tumor initiation (p=0.005) and reduced tumor volume (p=0.004), accompanied by decreased tumor angiogenesis (p=0.045). Importantly, no systemic toxicity or significant changes in weight were observed. Conclusion: By targeting angiogenesis, the KLH-AM mRNA vaccine effectively impaired tumor growth in melanoma models. These results highlight AM as an important pro-angiogenic factor driving tumor vascularization and support further development of AM-directed mRNA therapeutic vaccination as a strategy to disrupt angiogenesis-dependent tumor progression.This study was funded by Agencia Estatal de Investigación (AEI, Spain)’s project PID2022-136735OB-I00. Citation Format: Srdan Tadic, Laura Ochoa-Callejero, Judit Narro Íñiguez, Josune García-Sanmartín, Alfredo Martínez. An mRNA vaccine targeting angiogenesis elicits a robust immune response and inhibits tumor growth and angiogenesis in two mouse melanoma models abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4783.

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