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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: 1067; Downloads: 6
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Abstract: Background. Long term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures.Materials and methods. Human skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin - 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death.Results. Compared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70).Conclusions. Our results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions.
Keywords: myoblasts, irradiation, proliferation, interleukin 6, muscle regeneration, apoptosis
Published in RUP: 30.12.2015; Views: 5482; Downloads: 156
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