Matti Sällberg

We have studied viral hepatitis as a cause of cancer for almost 25 years. We have previously developed a therapeutic vaccine against hepatitis C virus which we tested in a phase I study on humans. We have used this knowledge and experience to develop a vaccine against COVID-19 in less than 3 years, which is now being tested in a phase I study on humans. We are now using all this experience and knowledge in our development of vaccines and immunotherapies against, above all, HBV and HDV. You cannot get rid of these viruses through today's treatment, and vaccines or immunotherapy are probably the best long-term ways to get the body to control these infections and reduce the risk of cancer. Chronic infections with HBV, HDV, and previously also HCV are leading causes of liver cancer globally. Today, HCV can be cured in >90% of all patients with a three-month treatment, but some develop liver cancer despite having cured the infection. Here we need to increase knowledge of how HCV establishes chronic infection and causes cancer. For HBV and HDV, new treatments are needed that lead to a so-called functional cure, i.e. you do not get rid of the infection but the body's immune system controls the infection, whereby the risk of cancer is greatly reduced. In addition, no further treatment is required. Thus, one strategy is to activate the body's immune response. During this period, we hope to be able to develop our treatments against HBV and HDV all the way to a clinical study in humans to see that the treatment activates the immune system as well in humans as in the animal models we have evaluated. our therapeutic vaccine can prevent co-infection with HBV and HDV, and also prevent mice with chronic HBV infection from being infected with HDV as well. The last is a big problem in countries in Asia. HDV shortens the time to serious liver disease by 75% compared to having only HBV. Thus, we see that our vaccines can be used to treat HBV and HDV, and also to prevent HDV infection.

The proposed doctoral program in advanced therapies (DPAT) focuses on preclinical development and clinical adoption of advanced therapy medicinal products (ATMP), a new class of drugs based on cells, genes or engineered tissues with great potential to effectively treat, or cure, a wide range of diseases. Today, patient access to ATMPs is limited by a lack of personnel with the knowledge of the field needed for these drugs to become routine clinical practice. A coordinated effort to ensure education of health care professionals is needed.DPAT targets teachers within programs relevant to the topic

medicine and dentistry, nursing, pharmacy and biomedical analyst education. The curriculum builds on the core doctoral training programs, complemented by newly co-developed courses and education activities about the ATMP development chain from research, via translation to implementation in health care, including manufacturing, quality control, regulatory and legal aspects, health economics, ethics, and entrepreneurship.DPAT is a national initiative by five Swedish universities, coordinated by Lund University. The universities contribute with their areas of strength and excellent research milieus within ATMP, as well as collaboration with internationally leading institutions in Europe and the US.By educating the teachers and connecting them closer to research, the doctoral program will significantly strengthen Sweden’s competence in this important field of tomorrows Health Care.

Hepatitis B, C and D viruses are leading causes of serious liver damage and cancer. We intend to develop new immunotherapies and vaccines against these to minimize cancer risk and improve treatment results. We work a lot with so-called genetic vaccines, i.e. the vaccine consists of part of the genetic material for viruses. When the genetic vaccine is taken up in our cells, they will produce the vaccine protein that activates the immune system. The advantage of this type of vaccine is that it activates a broad immune system. We will now work on developing good genetic vaccines against Hepatitis B, C and D viruses to reduce the cancer risk. During the next three-year period, we hope to be able to start human studies with at least one of our vaccines. In a first study, we will test how the vaccine works in healthy volunteers. This will tell whether the vaccine is safe, what dose works best and whether it can activate the immune system that we think will be able to work against the infection. Our first goal is to test the therapeutic vaccine against hepatitis B. If it is safe and works well, we will also test it for the treatment of hepatitis D. We hope that our research will lead to better treatment of chronic hepatitis B, C and D virus infections. We do this by developing better models to test our vaccines in and by developing completely new vaccines. If we can test our vaccines in clinical phase I, II and III studies, this can show whether these can improve the treatment of these viral infections and thus reduce the risk that they lead to liver cancer.

Chronic infections caused by hepatitis B virus (HBV) and hepatitis D virus (HDV) are a leading cause of liver cancer. For chronic HBV, there is currently a lifelong treatment that suppresses the viral proliferation but does not penalize the infection. For HDV, there is only 24 months of interferon treatment which only cures about 25%. Thus, there is a great need for new treatments for HBV and HDV. We intend to develop new immunological treatments for these infections. We are working on developing a treating vaccine against chronic HBV and HDV infection. This is supposed to be an addition to today's treatment. We start with a combination vaccine against HBV and HDV as a treatment for chronic HBV infection. In the studies that have begun, we have been able to show that the vaccine activates a T cell response to HBV and HDV as well as antibodies that prevent HBV / HDV from infecting new cells, so-called neutralizing antibodies. We intend to identify the best of 10 different vaccine candidates that are then developed for clinical trials in humans. In parallel with this, we also develop more experimental treatment principles. We hope that our research will lead to the treatment of chronic HBV and HDV infections being improved so that we can reduce the risk of developing cancer and serious liver damage. We believe that the vaccine we develop can give the infected control over the infection by reducing the number of cells that are infected and knocking out the cells already infected. If we succeed, this can lead to reduced suffering and reduced healthcare costs.

Chronic infections caused by hepatitis B virus (HBV) and hepatitis D virus (HDV) are a leading cause of liver cancer. For chronic HBV, there is currently a lifelong treatment that suppresses the viral proliferation but does not penalize the infection. For HDV, there is only 24 months of interferon treatment which only cures about 25%. Thus, there is a great need for new treatments for HBV and HDV. We intend to develop new immunological treatments for these infections. We are working on developing a treating vaccine against chronic HBV and HDV infection. This is supposed to be an addition to today's treatment. We start with a combination vaccine against HBV and HDV as a treatment for chronic HBV infection. In the studies that have begun, we have been able to show that the vaccine activates a T cell response to HBV and HDV as well as antibodies that prevent HBV / HDV from infecting new cells, so-called neutralizing antibodies. We intend to identify the best of 10 different vaccine candidates that are then developed for clinical trials in humans. In parallel with this, we also develop more experimental treatment principles. We hope that our research will lead to the treatment of chronic HBV and HDV infections being improved so that we can reduce the risk of developing cancer and serious liver damage. We believe that the vaccine we develop can give the infected control over the infection by reducing the number of cells that are infected and knocking out the cells already infected. If we succeed, this can lead to reduced suffering and reduced healthcare costs.

Co-infections in the liver caused by hepatitis B and D virus (HBV / HDV) often have a serious course. HDV can only multiply in liver cells that are already infected with HBV. HBV today requires lifelong treatment, but against HDV there is no good treatment. Thus, there is a great need to develop new treatments for HBV and HDV. This project focuses on developing new treatments for HBV and HDV. We have previously developed this type of treatment for hepatitis C and therefore believe that we have very good conditions for doing this also against HBV and HDV. We will produce so-called genetic vaccines, and gene therapy, to produce T cells that selectively recognize and kill liver cells infected with HBV or HDV. This makes HBV infected that they can hopefully end their lifelong treatment with antivirals as the body's own immune system controls viruses. For HDV, we hope that the infection will heal completely, or prevent it from occurring. To be able to do this in a safe and good way, attempts must be made in mouse models. We will develop a new mouse model that is more similar to human as the mouse will have human liver cells. We hope, of course, that we will be able to develop effective treatments for HBV and HDV to reduce, or even eliminate, the risk of liver cancer caused by these viruses. There are studies showing that both HBV and HDV can be controlled with a good T cell response. Thus, our goal is to be able to treat patients with chronic HBV and / or HDV in a rather near future with antigen activation of T cells with vaccine, or redirection of T cells via gene therapy. Our treating vaccine against HBV is today close to clinic testing. We think we can soon be in the same position for HDV.