Workshop in the frame of the project 'New approach to active immunotherapy of Hepatitis C related cancer' LZP-2018/2-0308 will take place on Thursday, 25 February.
The goal of the project was to develop a prototype-active immunotherapy to complement directly acting antiviral drugs in treatment of chronic hepatitis C and treat HCV related liver cancer. Immunotherapy strategy was to target and eliminate HCV-infected cells, specifically malignant (transformed) hepatocytes. The immunotherapy was based on a conserved HCV antigen nucleocapsid (Core) protein and tumor-associated antigen involved in the early events in hepatocarcinogenesis, human telomerase reverse transcriptase (TERT), presented by synthetic genes (HCV/TERT-DNA). Studies were performed in collaboration with the group of Prof. Arvydas Laurinavičius, Public Institution Vilnius University Hospital Santaros Klinikos, Lithuania, governed by ethical permissions to research groups in RSU and VPC.
During two years of the project, we have designed and synthesized prototype DNA vaccines against TERT, and nucleocapsid (core) protein of HCV, characterized their immunogenicity in mice, and defined molecular determinants of their immunogenicity. Their combination in a multi-gene vaccine was tested, to find incompatibility of the components, requesting a change of vaccination strategy. Further, stable expression of TERT was achieved in murine tumor cells, allowing to generate murine models for testing of the protective potential of prototype DNA vaccine against TERT. Similar models are in development for HCV. TERT, but not HCV Core DNA immunization was shown to effectively protect mice from challenge with TERT expressing tumor cells. In parallel, we have characterized TERT expression in hepatocellular carcinomas, and found patterns unique for HCV-related cancer, motivating the use of TERT as the basis of therapeutic DNA vaccine against HCV-related HCC. Altogether, our results shift the focus in HCC vaccine development from viral to tumor-specific antigens, such as TERT, and lay grounds to further development of TERT based cancer vaccines.
Anyone interested are welcome to join the meeting via Zoom. Please e-mail Maria[pnkts]Issagouliantisrsu[pnkts]lv at your earliest convenience for the Zoom link wich will be sent out on Wednesday, 24 February.
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