1. A virus based vaccine combined with IL12 gene therapy eradicates aggressive melanomaNuša Brišar, Katja Šuster, Simona Kranjc Brezar, Andrej Cör, 2025, original scientific article Abstract: Our study introduces a novel bacteriophage-based vaccine strategy and evaluates its antitumor efficacy, both as a standalone therapy and in combination with gene electrotransfer (GET) of interleukin-12 (IL-12) plasmids. Using phage display technology, we produced engineered M13 bacteriophages expressing tumour peptides MAGE-A1, gp100, or MART-1/MELAN-A on the surface of the capsid. The therapeutic potential of bacteriophage vaccination alone or in combination with GET IL-12 was tested in vivo in a mouse malignant melanoma model. Response to treatment was further characterized by histological and immunohistochemical analyses of tumour tissue. No negative side effects were observed during treatment in mice. Engineered bacteriophage therapy significantly delayed tumour growth. GET IL-12 contributed to the therapeutic effect of engineered bacteriophages and increased tumour growth delay. Both therapies had a synergistic effect and led to complete responses in 30% of cases. Histological and immunohistochemical analyses have shown that both bacteriophage monotherapy and, especially in combination with GET IL-12, activate the immune system and increase the proportion of necrosis and the infiltration of macrophages, CD4 + and CD8 + T lymphocytes in tumours. For the first time, a cocktail of three engineered M13 bacteriophages displaying different melanoma-associated antigens with intratumoral IL-12 gene electrotransfer were applied, demonstrating a synergistic therapeutic effect in a highly aggressive melanoma model. Nanotechnological approaches, such as the use of genetically engineered bacteriophages, offer promising new avenues for the development of anti-tumour vaccines.
Keywords: immunotherapy, bacteriophages, bacteriophage display technology, bacteriophage vaccine, interleukin, gene electrotransfer, malignant melanoma
Published in RUP: 16.06.2025; Views: 961; Downloads: 6
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2. Endoglin (CD105) silencing mediated by shRNA under the control of Endothelin-1 promoter for targeted gene therapy of MelanomaNataša Tešić, Urška Kamenšek, Gregor Serša, Simona Kranjc Brezar, Monika Savarin, Urša Lampreht Tratar, Véronique Préat, Gaëlle Vandermeulen, Miha Butinar, Boris Turk, Maja Čemažar, 2015, original scientific article Abstract: Endoglin (CD105), a transforming growth factor (TGF)-% coreceptor, and endothelin-1, a vasoconstrictor peptide, are both overexpressed in tumor endothelial and melanoma cells. Their targeting is therefore a promising therapeutic approach for melanoma tumors. The aim of our study was to construct a eukaryotic expression plasmid encoding the shRNA molecules against CD105 under the control of endothelin-1 promoter and to evaluate its therapeutic potential both in vitro in murine B16F10-luc melanoma and SVEC4-10 endothelial cells and in vivo in mice bearing highly metastatic B16F10-luc tumors. Plasmid encoding shRNA against CD105 under the control of the constitutive U6 promoter was used as a control. We demonstrated the antiproliferative and antiangiogenic effects of both plasmids in SVEC4-10 cells, as well as a moderate antitumor and pronounced antimetastatic effect in B16F10-luc tumors in vivo. Our results provide evidence that targeting melanoma with shRNA molecules against CD105 under the control of endothelin-1 promoter is a feasible and effective treatment, especially for the reduction of metastatic spread.
Keywords: melanoma, electroporation, endoglin (CD105), endothelin-1, gene therapy
Published in RUP: 14.10.2015; Views: 5835; Downloads: 135
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3. Biological properties of melanoma and endothelial cells after plasmid AMEP gene electrotransfer depend on integrin quantity on cellsMaša Bošnjak, Lara Prosen, Tanja Jesenko, Tanja Blagus, Boštjan Markelc, Maja Čemažar, Céline Bouquet, Gregor Serša, 2013, original scientific article Keywords: antiangiogenic, integrins, gene electrotransfer, human endothelial cells, murine melanoma cells, plasmid AMEP
Published in RUP: 15.10.2013; Views: 5242; Downloads: 121
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