ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1604156
This article is part of the Research TopicmRNA Design, Manufacturing, Delivery, and Applications in MedicineView all 4 articles
An RNA vaccine against adrenomedullin reduces angiogenesis and tumor burden in a syngeneic metastatic melanoma mouse model
Provisionally accepted
- Centro de Investigación Biomédica de La Rioja, Logroño, Spain
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Adrenomedullin (AM) is an autocrine/paracrine growth factor as well as a crucial regulator of angiogenesis and immune response. AM is overexpressed by most solid tumors, which makes it a good target for anti-tumor therapy. In this study, we designed and tested an mRNA vaccine directed against a fusion antigen composed by a small piece of keyhole limpet hemocyanin (KLH), as a hapten, and mouse AM. The in vitro-synthesized mRNA was encapsulated in lipid nanoparticles (LNPs) and injected in C57BL/6 mice. Empty LNPs were used as a negative control. After five immunizations, B16-F10 melanoma cells were injected through the tail vein to induce lung metastases. In addition, transgenic mice expressing green fluorescent protein in the blood vessels (SMAA-GFP) were also immunized with both LNP types to assess the potential side-effects of the vaccine on normal blood vessels. Antibody titers against AM and the number of CD8 + T cells were significantly higher in AMimmunized mice than in negative controls. Furthermore, the number and size of the lung metastases, as well as the number of blood vessels, were significantly reduced in the AM-immunized group. In addition, no significant differences were observed in the number and distribution of existing blood vessels after immunization of the SMAA-GFP animals. In summary, we have shown that a mRNA vaccine against the fusion KLH-AM peptide was able to break peripheral immunotolerance and induce a specific response against the angiogenic factor AM thus reducing tumor burden in the absence of disturbances to normal blood vessels.
Keywords: Adrenomedullin, Angiogenesis, mRNA vaccine, Melanoma, Lung metastases, Lipid nanoparticles
Received: 01 Apr 2025; Accepted: 19 May 2025.
Copyright: © 2025 Tadic, Ochoa, Narro Íñiguez, García Sanmartín and Martínez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Alfredo Martínez, Centro de Investigación Biomédica de La Rioja, Logroño, Spain
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