Tumor formalin fixed vaccines and secondary immune response to elicit a therapeutic immune response in solid tumors

Abstract

In the fields of treatment of metastatic tumour disease and its recurrence there were not a lot of significant success. It seems that this was mainly due to complexity of tumour disease, effect of the tumour microenvironment and high adaptability of tumour cells as well as the most therapeutic approaches are targeting singular tumour protein or gene which can be easily self-modified that as result have therapy failure and progression of the tumour. In this study, by developing of the autologous tumour formalin fixed vaccines we tried to tackle these main issues in the treatment of solid tumours. We have used two murine models of the carcinogenesis in order to get better insight in the features of possible anti-tumour immune response. Tumour antigens were obtained from the animal’s tumour tissue biopsies, processed and injected into the animals alone or along with the Rotarix. First immunisation was performed with the Rotarix or the AFFTV, while different combinations of the AFFTV and Rotarix were used for the second immunisation, so that the secondary immune response could be obtained. In the chemical carcinogenesis model, AFFTV made of tumour tissue biopsy in combination with a Rotarix induced a significant increase in the infiltration of lymphocytes in the primary tumour (liver), in vaccinated animals as compared to control. In the transplantable model of carcinogenesis, AFFTV made of the tumour cell line alone, when administered via subcutaneous route, have induced the highest score of lymphocyte infiltration in the subcutaneous tumour as well as in the lungs, as compared to other combinations. However, in the second experiment, the AFFTV made with the combination of tumour tissue biopsy and tumour cell line, injected with the Rotarix intraperitoneally, have induced highes lymphocyte infiltration in the subcutaneous tumour as compared to other combinations however the median survival of this group was the lowest as compared to other. The flow cytometry analysis was performed in order to quantify the CD8+ T cells. It was observed that amount of these cells is highest in the control group as compared to vaccinated one, seven days after second immunisation with the combination of the AFFTV and the Rotarix, intraperitoneally. The small sample size and certain effect that AFFTV vaccine formulation induced provides the rationale for further study with larger sample size.