New Data on the Influence of the HPV16 E2 Early Protein Obtained in Plant Expression Nanosystems on Tumor Tissues of Female Mice Induced by Injection of HeLa Cancer Cells in Hip Muscle

Abstract

The prospects of creating a therapeutic anti-cancer vaccine using the HPV16 E2 regulatory gene have been investigated. An expression system for the synthesis of early antigenic proteins HPV16 E2, of high-risk papillomavirus based on transgenic tomato fruits has been developed. To induce malignant transformation of tissues, female mice at an age of 6 months were injected with a suspension of HeLa cancer cells into the hip muscle. In 1 month, blood was collected from half of the mice, splenocytes were isolated from the spleen, and alterations in internal organs, including the lungs, were studied. The other half of the HeLa-injected mice received a peroral inoculation with vaccine material from tomatoes with HPV16 E2 (500 mg of E2 protein per mouse). In 1 month, blood was collected from the vaccinated mice, splenocytes were isolated, and alterations in internal organs were investigated. After the injection of HeLa tumor cells, the lungs increased in size and contained various tumors. The mice with HeLa administration and the peroral HPV16 E2 vaccination had no specific abnormalities in the size and morphology of the lungs. Comparing the levels of interferon, CD4 and CD8 T lymphocytes, as well as the cells that interacted with anti-granzyme B and anti-perforin antibodies, showed that HPV16 E2 vaccination increased the number of cells that bind antibodies to interferon, CD4 and CD8 T lymphocytes, granzyme B, and perforin by 1.5–2 orders of magnitude. The HPV16 E2 protein can significantly suppress the proliferation of cancer cells and can be used for the creation of a therapeutic vaccine against a cancer caused by the most highly oncogenic type of papillomavirus, HPV16.