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

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.

Tadic, Srdan et al.·International journal of molecular sciences·2025·
RPEP-137432025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Not classified
Evidence
Not graded
Sample
Not reported

What This Study 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.

Key Numbers

How They Did This

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.

Why This Research 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.

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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
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
Evidence Grade:
Preclinical with robust statistical outcomes and important negative controls (TME, toxicity). Strong proof of concept.
Study Age:
Published in 2025.
Original Title:
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.
Published In:
International journal of molecular sciences, 26(21) (2025)
Database ID:
RPEP-13743

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked 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 More on RethinkPeptides

Related articles coming soon.

Cite This Study

RPEP-13743·https://rethinkpeptides.com/research/RPEP-13743

APA

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

MLA

Tadic, Srdan, et al. "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, 2025. https://doi.org/10.3390/ijms262110745

RethinkPeptides

RethinkPeptides Research Database. "A Stable RNA Vaccine Against the Regulatory Peptide Adrenome..." RPEP-13743. Retrieved from https://rethinkpeptides.com/research/tadic-2025-a-stable-rna-vaccine

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.