mRNA vaccine targeting the regulatory peptide adrenomedullin reduces tumor blood vessels and melanoma growth | Research

The takeaway

An mRNA-LNP vaccine encoding KLH-adrenomedullin fusion antigen delayed melanoma initiation, reduced tumor volume (p=0.0004), decreased tumor vessel area (p=0.028), and increased anti-AM IgG and CD8+ T cells without immunosuppressive TME changes.

Tumor volume reduced p=0.0004
mRNA vaccine targeting the pro-tumoral peptide adrenomedullin achieved dramatic tumor reduction without immunosuppression—combining mRNA technology with peptide targeting

What the researchers found

Tumor initiation delayed (p=0.005). Volume reduced (p=0.0004). Vessel area decreased (p=0.028). ↑Anti-AM IgG (p=0.033). ↑CD8+ T cells (p=0.049). No TME immunosuppression. No toxicity/weight loss. Stable at 4°C >1 month.

Why it matters

Targeting regulatory peptides with vaccines is a novel immunotherapy approach. Adrenomedullin vaccination achieved anti-tumor effects without the immunosuppressive side effects that plague many cancer immunotherapies.

How the study worked

C57BL/6J mice. mRNA-LNP vaccine (KLH-AM fusion). 4-dose immunization → B16-F10 melanoma injection → booster. Tumor volume, angiogenesis, immune infiltration, Ki67 proliferation analysis.

What this study cannot tell us

Mouse melanoma model. Subcutaneous tumors (not metastatic in this study, though prior study tested metastatic). Single tumor type. Prophylactic rather than therapeutic setting.

How to read the evidence

Preclinical with robust statistical outcomes and important negative controls (TME, toxicity). Strong proof of concept.

When this study was published

Published in 2025.

The bigger picture

Peptide-targeted mRNA vaccines represent a convergence of two cutting-edge technologies: mRNA vaccine platforms (proven by COVID) and peptide hormone targeting for cancer. This could extend to other tumor-promoting peptides.

Questions still open

Would the vaccine work against established metastatic melanoma?
Could AM-targeted vaccines treat other AM-expressing cancers?
Is the 4°C stability sufficient for clinical distribution?

Common questions

Can an mRNA vaccine fight cancer?

This study shows yes—an mRNA vaccine targeting the peptide adrenomedullin (which helps tumors grow blood vessels) significantly reduced melanoma tumor volume and delayed tumor formation. Unlike many cancer treatments, it did not suppress the immune system, and the vaccine was remarkably stable at refrigerator temperature.

What is adrenomedullin and why target it?

Adrenomedullin (AM) is a peptide that melanoma tumors produce to grow new blood vessels, spread, and proliferate. By vaccinating against AM, the immune system creates antibodies that block this peptide, starving tumors of blood supply and slowing their growth—an anti-angiogenic approach using the body's own immune response.

Read the original research

A Stable RNA Vaccine Against the Regulatory Peptide Adrenomedullin Reduces Angiogenesis and Tumor Burden in a Subcutaneous Melanoma Model Without Inducing an Immunosuppressive Tumor Microenvironment.

International journal of molecular sciences, 26(21)

View on PubMed ↗Publisher’s paper ↗

Citation

Tadic, Srdan; García-Sanmartín, Josune; Narro-Íñiguez, Judit; Martínez, Alfredo. (2025). A Stable RNA Vaccine Against the Regulatory Peptide Adrenomedullin Reduces Angiogenesis and Tumor Burden in a Subcutaneous Melanoma Model Without Inducing an Immunosuppressive Tumor Microenvironment.. International journal of molecular sciences, 26(21). https://doi.org/10.3390/ijms262110745