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New approach to active immunotherapy of Hepatitis C related cancer (LIVE®VAC)

Project/agreement No.
lzp-2018/2-0308
Project funding
200 000.00 EUR
Project manager
Maria Issagouliantis
Project realization
01.12.2018. - 01.12.2020.

Aim

Project goal is to develop a prototype active immunotherapy to complement directly acting antiviral drugs in treatment of chronic hepatitis C, which would target and eliminate HCV-infected cells, specifically malignant (transformed) hepatocytes and lymphocytes. The immunotherapy will be based on a conserved HCV antigen nucleocapsid (Core) protein and tumor-associated antigen involved in the early events in hepatocarcinogenesis, human telomerase reverse transcriptase, presented by synthetic genes (HCV/TERT-DNA).

Description

Hepatitis C virus causes hepatocellular carcinomas/HCC and triggers Non-Hodgkin´s B-cell lymphomas/NHL affecting millions of people and presenting a devastating burden to health-care systems all over the world. Directly acting antiviral drugs cure HCV infection, but cannot reliably cure liver cancer, or lymphoid malignancies. Besides, they induce resistance, which would eventually limit their use. Recent clinical trials demonstrated possibility of active cancer immunotherapy. We will develop such therapy against HCC and NHL based on plasmid DNA. DNA-vaccine will target HCV core, and early tumor-associated antigen human telomerase reverse transcriptase/TERT. DNA-vaccine will be reinforced by Toll-Like Receptor 7/8 ligand and check-point inhibitors as PD-1/PD-L1. Their combination will be introduced intratumorally to enhance efficacy and reduce off-side toxicities. Combination will be tested for immunogenicity in two mouse strains. Effector response will be evaluated in the murine models of human cancer responsive and refractory to immunotherapy. Proof of concept will be to demonstrate the capacity of immune response to lyse HCV-, TERT- and HCV/TERT-expressing tumor cells, protect mice from tumor challenge and/or cure animals from HCV/TERT-(co)expressing tumors and their metastases. Project will integrate basic research with R&D of a prototype immunotherapeutical. This novel approach has direct relevance to immunotherapy of cancer caused by other tumorigenic human viruses.

Project output

Workshop Immunotherapy of cancer 

Workshop Immunotherapy of Cancer was held on 13 June 2019 in Senate Hall at Rīga Stradiņš University. The seminar is part of the project New approach to active immunotherapy of Hepatitis C related cancer (LZP-2018/2-0308).
One of the world’s leaders in the field of biotechnology research, Professor Edward Rybicki of the University of Cape Town, gave a lecture Therapeutic cancer vaccines made in plants. At the workshop also attended researchers from Sweden, Russia and Latvia with information on the results of recent research in the development of targeted cancer immunotherapy. 

Workshop6.jpg

 

Agenda and presentations: 

1.Rybicki.JPG

Invited lecture Therapeutic cancer vaccines made in plants
Ed Rybicki,
Molecular & Cell Biology Department, University of Cape Town, South Africa
Effective therapeutic vaccines for human cancers would be a highly sought-after solution to often intractable disease problems. While there are presently a number of exciting possibilities in this regard - and specifically, the recent successes with monoclonal antibody therapies - the cost of production of complex biologics limits their application in especially developing countries, where much of the problem resides. The use of plants for the production of such biologics is becoming increasingly feasible and increasingly popular, and could revolutionise the provision of such medicines in the wider world. This presentation will cover plant production of cancer therapeutics in general, with a particular focus on human papillomavirus disease where some signal successes have been obtained.
 

Presentation

13.Gordeychuk.JPG

Nonhuman primate models for preclinical testing of cancer vaccines
Ilya Gordeychuk,
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow, Russia
 

Presentation

16.Isaguliants.JPGTumorigenic effects of HIV antigens mediated through the induction of oxidative stress
Maria Isaguliants,
Riga Stradiņš University, Riga, Latvia, and Karolinska Institutet, Stockholm, Sweden
 
27.Zajakina.JPG

Reprogramming of macrophages for immunotherapy of cancer
Anna Zajakina
, Biomedical Research and Study Centre, Riga, Latvia
 

Presentation

32.Kurlanda.JPGMultifunctional immune response against tumor associated antigen, telomerase reverse transcriptase (TERT) induced in mice electroporated with TERT DNA
Alisa Kurlanda
, Riga Stradiņš University, Riga, Latvia
 
46.Jansons.JPG

Optimization of DNA vaccines against hepatitis C virus targeting its nucleocapsid (core) protein 
Juris Jansons,
Riga Stradiņš University, and Biomedical Research and Study Centre, Riga, Latvia
 

Presentation

54.Kluska.JPG

University of Lodz
Magdalena Kluska
, University of Lodz, Lodz, Poland 
 

Presentation