The Study Of Cancer Immunotherapy And Prevention By Nanovaccines Loaded Cancer Cell Lysates At Both Inner And Outer Part

Cancer vaccine is one of the important methods of cancer immunotherapy.Cancer vaccines can modulate the body’s immune system and activate the immune system to produce tumor-specific immune responses.The antigen component loaded by cancer vaccines is the key to induce cancer-specific immune responses.Due to the individual differences and diversity of cancer antigens,the efficacy of cancer vaccines prepared from a single antigen component or a limited number of antigen components is relatively limited.The tumor cells themselves are the best cancer antigen library and can be used as antigen sources for cancer vaccines.In this study,the whole-tumor-cell was used as the antigen components in our nanovaccines,so that the nanovaccines can cover a wider and more diverse spectrum of tumor antigens.In order to enable the nanovaccines to be efficiently uptake by antigen-presenting cells(APCs),we controlled the particle size of the nanovaccines to approximate 320 nm;In order to enable the activation of antigen-specific T cells more efficiently and even at a lower concentration of antigen epitopes,we co-encapsulated the immune adjuvant Poly(I:C)with the antigens in the nanovaccines;In order to load as many antigens as possible into the nanovaccines for the induction of better immune responses,we loaded antigens both inside and on the surface of our nanovaccines.Studies have shown that the nanovaccines constructed in this research can be taken up by APCs and release the payload in APCs.The anti-tumor studies in the mouse melanoma and triple-negative breast cancer(TNBC)model showed that nanovaccines had a good therapeutic effect for different kinds of cancer.In melanoma mouse model,25%of the mice were completely cured after treatment and when we combined nanovaccines withαPD-1 antibody,the results demonstrated a synergistic inhibitory effect and improved the cure rate to approximate 40%.Moreover,the immune memory developed in the cured mice allowed the mice to resist the second time of tumor inoculation.T cell analysis and tumor microenvironment(TME)analysis showed that nanovaccines induced tumor-specific T cells,activated the adaptive immune response and innate immune response against tumor cells,and increased the formation of tertiary lymphatic structures at the tumor site.Cancer prevention studies showed that the nanovaccines could efficiently prevent lung cancer(100%)and melanoma(70%)in mice.Furthermore,we also found that the prevention effect of nanovaccines is achieved by inducing memory T cells(especially central memory T cells(Tcm))in lymph nodes,spleen and peripheral blood.Mouse weight monitoring and H&E staining demonstrated that our nanovaccines had no side effects on mice.In summary,the nanovaccines can prevent and treat a variety of cancers in mouse models and is expected to provide a new solution for cancer prevention and immunotherapy.