Generating a mRNA vaccine to target tumor-mediated angiogenesis and metastasis

I am Srdjan Tadic, ESR7, and I am working under the supervision of Dr. Alfredo Martinez at Fundacion Rioja Salud (FRS).

My role in the DIRNANO Project is to test and quantify the possible anti-tumoral and anti-metastatic therapeutic efficacy of nanoparticle-based cancer vaccine candidates in vivo. Nanovaccines that are generated by other partners of the consortium and immunologically characterized will be tested in immunocompetent C57BL/6 mice using both xenograft and lung cancer metastasis mouse models.

After immunization with candidate nanovaccines, and after the antibody titers have been quantified, all mice will be tumor challenged. For tumor challenge we will be using melanoma cells (lines B16-F10 or 5555), injected in the flank area or in the tail vein (lung metastasis model). The tumor size will be regularly measured. Eventually the lung samples will be collected and lung metastases number will be assessed. Lungs will be weighted, fixed, and paraffin-embedded. Sections will be stained with hematoxylin-eosin and specific fluorescent antibodies to localize different immune cell types.

Additionally to my responsibilities in the consortium, I am trying to develop an mRNA vaccine targeting tumor-related angiogenesis. As a target, I am using adrenomedullin (AM) as one of the crucial regulators of angiogenesis that acts as an autocrine/paracrine growth factor. Its expression is highly up-regulated and favored by hypoxia in various solid tumors, while it is minimal in normal tissue, which makes it a good candidate/target for anti-tumor therapy.

Aim of the project

The aim of my project is to design a mRNA vaccine that can induce and direct immune response towards AM which, as a result, should have an anti-angiogenesis effect and reduction/prevention of metastases. Since AM is a self-antigen, in order to elicit the immune response we will construct a fusion mRNA putting together AM and a large hapten. This mRNA will be incorporated into liposomes, as an adjuvant and carrier. After injection, we expect this mRNA to be delivered to different cell types, including muscle cells. This should result in the expression of the fusion peptide on the surface of these cells and recognition by immune cells, thus resulting in the initiation of an effective immune response. The immune response will be measured by ELISA and, once high antibody titers are demonstrated, animals will be challenged with tumor cells to investigate whether this approach can reduce tumor growth and metastasis.

 

Srdjan Tadic - Early Stage Researcher

Department of Oncology, Angiogenesis - University of La Rioja (Spain)

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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 956544
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