Lung cancers are often discovered after they have spread throughout the body. When this happens, patients must be treated with drugs. These drugs often shrink tumors but do not cure patients. The tumor cells that survive these drug treatments are known as “residual” cells. Residual cells eventually grow back, causing death. For this reason, we are very interested in discovering drugs that can kill residual lung cancer cells. Recently we discovered that residual lung cancer cells cannot survive without an enzyme called PKN2. We have access to a drug that blocks PKN2. Further, we already know that this drug is safe for patients. We are applying for grant funds to do three things. First, we will determine which residual lung cancers are most sensitive to this drug. Second, we will determine how this drug kills residual lung cancers. Third, we will determine how well this drug prevents lung cancer from relapsing in mice. Together, these studies will advance our understanding of residual lung cancer. They will also advance a new drug therapy that can be quickly translated to clinical trials by our team of expert doctors and scientists.
After successful treatments, cancer patients often dread their disease returning months or years down the road. Even a few cancer cells hidden in the body can find ways to grow again. We will find ways to block these cancer cells from mutating so that they cannot find ways to grow again. These studies seek to provide new ways to extend survival and improve quality of life.
Multiple myeloma is a type of cancer that affects plasma cells. This disease can lead to infections, kidney problems, and bone pain or fractures. There have been great improvements in the treatment of multiple myeloma in recent years. However, most people are still not cured by current therapy. Treatments that use the immune system have shown great promise. One important example is CAR T-cell therapy. CAR T cells are made by taking a patient’s T cells (a type of immune cell), and changing them so they can recognize and kill cancer cells. These cells are then given back into the patient by an intravenous infusion. CART cell therapy has resulted in dramatic improvements in outcomes for patients with multiple myeloma. Our group has studied a new combination approach to improve upon responses to CART cell therapy. We have developed a personalized cancer vaccines using a patient’s own cancer cells. To make the vaccine, a patients plasma cells are collected from the bone marrow and are combined with immune cells called dendritic cells, which help activate the immune system. In a national study, this vaccine was shown to be safe, could be made at centers across the country, and was shown to stimulate immune responses. In this new study will test the vaccine in combination with CAR T-cell therapy. This DC/MM fusion vaccine has the potential to stimulate a broad immune response, preventing the development of resistance and can expand the CART cells to enhance their durability and effect.
The Southeastern American Indian Cancer Health Equity Partnership (SAICEP) is a team made up of three cancer centers in North Carolina. These centers are working together to help lower cancer rates in American Indian communities. This year, with help from the V Foundation, SAICEP is starting a new project for Native youth and young adults, ages 16 to 30. The goal is to lower the risk of cancer by focusing on three things: getting the HPV vaccine, staying safe in the sun, and stop the use of unsafe tobacco products. To do this, SAICEP will work with the North Carolina Native American Youth Organization (NCNAYO). They will choose and train Native youth to become health ambassadors. These ambassadors will share important health information in their communities. SAICEP will also go to Native events across the state to talk with people and hand out materials about cancer health. At the end of the project, they will ask the youth and others what they learned and how the project helped. This project will help more young Native people stay healthy and avoid cancer in the future. It also gives Native youth a chance to lead and help their own communities.
Acute Myelogenous Leukemia (AML) is a fast-growing cancer of the blood and is the most common type in adults. Unfortunately, current treatments often don’t work well, and many patients get sick again or die. That’s why new and better treatments are needed. In our research, we looked at a protein that is found in large amounts on the outside of leukemia cells. Our earlier studies showed that this protein is needed for the cancer to grow. Because it’s on the outside of the cell, we can try to block it using special tools called antibodies. These antibodies attach to the protein and stop it from working. Here, we propose to develop an antibody that is able to target the protein and stop the cancer cells from growing. If we are successful, we plan to test the antibody in patients who are newly diagnosed or who haven’t gotten better with current treatments. This new antibody treatment could be a powerful new way to help people with AML live longer and healthier lives.
Immunotherapy is a type of cancer treatment that helps the body’s immune system fight cancer. It has changed how we treat many cancers. But not all patients benefit from it. So, we need new ways to make this treatment work better. One area of interest is the gut microbiome. This is the group of trillions of bacteria that live in our gut. These bacteria can affect how the immune system works and how well immunotherapy works. Our research, and that of others, has shown that people who respond to immunotherapy have different gut bacteria than those who do not. Diet plays a big role in shaping the gut microbiome, as the bacteria in our gut eat what we eat. We have shown that diet is linked to how well people respond to immunotherapy. In mice, changing the diet changed both the gut bacteria and the response to treatment. Now, we are testing if diet changes can help patients who are starting immunotherapy. We want to see if we can improve their gut bacteria and boost their immune response through their diet. If this works, it could be a simple and low-cost way to help more people benefit from immunotherapy. We also found that a plant-based, high-fiber diet lowers certain bile acids in the body; these acids may weaken the patient’s immune response. In this study, we will test if these bile acids can be used as a marker of the extent to which the diet and treatment are working.
Women with excess body weight are more likely to get breast cancer than women with a healthy weight. The effect of excess body weight is especially harmful to women with a family history of breast cancer. Excess body weight can cause many harmful effects to cells. By limiting or reversing these changes, we may be able to prevent breast cancer. We think that exercise or weight loss can decrease the risk of breast cancer by reducing damage to cells. This is very important as it may provide options for women who decide not to get prevention surgery. In the future, we will apply what we have learned to a clinical trial.
Funded with support from Hockey Fights Cancer in honor of Ben Stelter
Glioblastoma (GBM) is the deadliest adult brain cancer. Even with standard of care treatment, survival rates are low. A major challenge is that the brain’s protective barrier blocks most drugs. The tumor also weakens the immune system, making it harder for treatments to work. CAR-T cell therapy is a promising treatment that trains T cells, a special immune cell, to recognize and attack cancer cells. It works well in other cancers, but not GBM. Normally, T cells follow signals from proteins called chemokines and cytokines to locate and fight disease. However, GBM blocks these signals, stopping T cells from working properly. Our study will develop a new immune gene therapy using a harmless virus called AAV to help the immune system fight GBM. This therapy reprograms nearby brain cells (called astrocytes) to send signals that attract and activate immune cells, including CAR-T cells. Our gene therapy will deliver two key proteins: CXCL9 (which attracts T cells) and IL-2 (which helps them grow and stay active). This targeted approach ensures a steady immune response right at the tumor. We will combine this immune gene therapy with CAR-T cells to improve their ability to find, survive, and attack the tumor. Our research will study how AAV works in the brain, activates CAR-T cells, and which AAVs can be used in human clinical trials.
Funded by the V Foundation Chicago Epicurean in honor of The Debbie Jones Family
Cancer immunotherapy with checkpoint receptor inhibitors (ICIs) causes autoimmune side effects. These side effects occur in most patients treated with ICIs. These side effects are debilitating and difficult to treat. My goal is to find treatments for ICI side effects. I developed new mouse models where ICIs induce the same autoimmune side effects as in humans. I will use these models to understand why ICIs are toxic. I will also understand how to treat the side effects of ICIs.
Pancreatic cancer is one of the most difficult cancers to treat, with only about 1 in 10 patients living five years after diagnosis. New and more effective treatments are urgently needed. One promising option is CAR-T cell therapy, which uses a patient’s own immune cells to fight cancer. While this treatment works well in blood cancers, it has not been successful in solid tumors like pancreatic cancer. One major challenge is the environment around the tumor, which lacks nutrients and weakens the immune system. This makes it hard for immune cells to survive and do their job. Our research aims to solve this problem by using a single target to improve both the immune cells and the tumor environment. We have found that changing how immune cells use energy can help them stay stronger and last longer in the body. At the same time, targeting how cancer cells grow makes the tumor more vulnerable to attack. By combining these two strategies, we hope to improve how well CAR-T cells work against pancreatic cancer. With support from the V Foundation, we will test this approach in models of pancreatic cancer. If successful, this work could lead to better treatment options for people with pancreatic cancer and potentially other hard-to-treat cancers as well.
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