The effect of “early” proteins E2, E6 and E7 of papillomavirus of high-risk cancerogenous type HPV16 on cancer HeLa cells, inducing tumour growths in mice lungs

Abstract

The goal of investigation was the development of oral therapeutic vaccine against cancer on basis of antigenic regulatory protein HPV16 E2 encoded by the “early” hpv16 E2 gene.The aim. To study tumour growths in mice lungs inoculated with cancer HeLa cells and then vaccinated with vaccine material of transgenic tomato with the gene/protein HPV16 E2, and to study the activation of the immunogenesis of T-lymphocytes in mice after oral vaccination with HPV16 E2.Materials and methods. Proliferating cancer HeLa cells, mice peripheric blood mononuclear cells, splenocytes, intact and isolated lungs of mice were used in the study. Elispot was used for the evaluation of increasing of immunogenicity.Results. “Early” proteins HPV16 E6 or HPV16 E7 did not reveal any effect on HeLa cells. The regulatory antigenic “early” protein HPV16 E2 drastically degraded HeLa cells recorded by trypane blue. Four types of tumours were found in mice lung lobes placed in the suspension of cancer HeLa cells for 2–5 days: 1 – peripheral round tumours on epithelium, 2 – central tumours in the area of tracheal carina, 3 – pneumonialike peripheral cancer on lung lobes which was very similar to small-round-cell lung sarcoma with hyperchromic nuclei and 4 – Pancoast-like cancer in apical parts of lung lobe. Patterns of normal developed lung tissues were viewed on slices of lungs infected with HeLa in the presence of E2 simultaneously. The very high contents of γ‑interferon, CD4/CD8 T lymphocytes, T cell receptor and apoptotic enzymes: granzyme B, perforin and granulysine – were detected in blood and splenocytes of mice vaccinated with HPV16 E2.Conclusion. The study is promising for the development of an oral therapeutic vaccine based on a plant expression system (tomatoes) with the HPV16 E2 antigenic protein against lung cancer, cervical cancer and other types of cancer.