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Radboud University Medical Center has received funding from KWF and Alpe d'HuZes for three projects. These are a large research project by Jolanda de Vries and two high-risk projects by Milda Poceviciute and Laia Querol Cano.
Jolanda de Vries' project: preventing cancer in people with Lynch by vaccinating against proteins on the precursors of cancer cells. Theme immunotherapy, over 3 million.
In this study, people with Lynch Syndrome are being vaccinated to prevent cancer. People with Lynch Syndrome (LS) have an inherited predisposition to develop cancer at a young age (under 50). Optimal vaccination uses proteins that arise in normal cells just before they become cancer cells. If we can vaccinate against these pre-cancer proteins, the development of cancer is nipped in the bud. More than a decade ago, we vaccinated 23 people with LS against pre-cancer proteins using their own dendritic cells. In 9 people, we saw an immune response against a particular pre-cancer protein. None of these 9 people developed cancer, unlike the group that did not respond. In those, 50 percent developed cancer. This study uses multiple proteins to increase the number of patients with a positive immune response to prevent cancer in these patients.
Risk of colon and uterine cancer
About one in 370 Dutch people (40,000 to 50,000 people) have the LS. During their lifetime, depending on their mutation, they have a 25 to 70 percent risk of especially colon and uterine cancer. Despite regular screening for people who know they have LS, cancer sometimes develops. Cancer can be prevented with preventive vaccination, though. We are now focusing on LS but are at the very beginning of our ultimate goal of vaccinating all people against cancer.
Loaded dendritic cells
Dendritic cells (DC) are capable of activating the immune system. DC are grown in the laboratory from the cells of the LS carrier itself and loaded with pieces of newly formed proteins that are found on pre-cancerous cells but not on healthy tissue. In this study, we plan to vaccinate 23 people with LS who have not had cancer. The immune response to newly formed proteins will be measured in skin biopsies. These 23 people with LS will continue to participate in the regular screening program so that we can follow the clinical course.
Admission to the market
The study aims to demonstrate that DC vaccination with multiple pre-cancer proteins is safe and well tolerated for people with LS, that more than 40 percent of vaccinated people with LS generate an immune response, and that those patients with immune responses are protected against cancer development for a long period of time. If the outcome of this study is positive, we have sufficient data to qualify for funding from the Health Care Institute for a large follow-up study. This study will be designed on the advice of the Medicines Evaluation Board (CBG) to obtain market approval making this therapy available to all patients with LS.
THE TWO HIGH-RISK PROJECTS:
Milda Poceviciute's high-risk project: Predicting vulvar cancer by adding artificial intelligence to pathologist's assessment of tissue biopsy. Topic biomarkers, over 1 ton.
Pubic lip cancer (vulvar cancer) is a rare cancer that is becoming increasingly common. Treatment usually consists of surgery on the vulva with the removal of 1 or more lymph nodes from the groin. This surgery can have a significant impact on both psychological and sexual quality of life. A small proportion of vulvar cancer cases are caused by the human papillomavirus (HPV) we know from cervical cancer. Hopefully, this is decreasing due to HPV vaccinations.
Usually, vulvar cancer develops in women with the skin disease lichen sclerosus (LS), with unknown cause. Women with LS often have itching or pain symptoms and about a four percent chance of developing vulvar cancer. LS can be treated well with hormone ointments but is not curable. With LS, a preliminary stage called differentiated VIN (dVIN) can develop first, which can lead to vulvar cancer much faster. Therefore, dVIN spots are often removed in hopes of preventing cancer. Currently, it is not easy to predict which women will develop vulvar cancer. Therefore, patients with LS and dVIN are often monitored regularly by a physician for life. The goal of this project is to be able to predict which patients with LS and dVIN are at high risk for vulvar cancer.
Laia Querol Cano's high-risk project: Galectins as a new cancer immunotherapy. Theme immunotherapy, over 2 tons.
Immunotherapy is a relatively new cancer treatment that allows the immune system to better destroy cancer cells. Unfortunately, this does not work in all cancer patients, and more insight is needed to develop new strategies to improve therapy. The tumor microenvironment can inhibit immune cells, stimulating disease progression. Dendritic cells (DCs) are immune cells in our body that are essential for initiating an immune response against tumors. DCs are already currently being used in tumor vaccines where patients are vaccinated with the body's own DCs in clinical trials within our department. We have found that loss of galectins in DCs is an important factor underlying immune escape from cancer. Further understanding of underlying mechanisms is critical for the development of new immunotherapies.
Galectins, a family of sugar-binding proteins, bind specific immune receptors that are essential for cancer immunity. Our studies show that galectins are required for DC migration and T cell activation, both of which are indispensable in cancer defense. We found that the amount of galectins in DCs is directly related to the survival of patients with skin cancer or lung cancer. Tumor cells can down-regulate galectins in DCs, which impairs DC function and impairs anti-tumor immune responses. Our results support the hypothesis that restoring galectins on the membrane of DCs stimulates the anti-cancer immune response. As a result, galectins may be used as a novel and promising anti-cancer immunotherapy. The goal of this research project is to understand how galectins promote anti-tumor DC function in order to use galectins as a new immune therapy against cancer.
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