Alison Ringel, PhD

Immune therapy is a cancer treatment that turns on killer T cells to attack the tumor. It is a major advance in cancer care. As it is less damaging to healthy tissue than chemotherapy, it has fewer side effects. Most importantly, it can help patients with advanced disease who had few options before. However, many patients do not benefit from immune therapy. The reasons why are not fully understood. Cancer affects people of all ages, but it is much more common in the elderly. T cells are key to the success of immune therapy, but aged T cells do not work as well as young ones. We have discovered that a signal important for T cell function is lost as people age. The loss happens even before a tumor appears. As tumors grow, aging makes even more T cells lose this signal. Our research will test whether the loss of this signal explains why older patients do not respond to immune checkpoint therapies. We will explore ways to restore this signal to improve treatment outcomes. Through this research, we hope to make immune therapy effective for more patients, especially older adults who face the highest rates of cancer.

Anirban Das, MBBS, MD, DM

Funded by the Dick Vitale Pediatric Cancer Research Fund

Glioblastoma is a cancerous brain tumor and the major cause of cancer-related death in children, teens, and young adults. Standard treatments like surgery, chemotherapy, and radiation don’t work here. Our international consortium found a group of glioblastomas caused by problems with how DNA is copied. These are called replication repair deficient (RRD)-gliomas. We showed that they have many mutations and can respond after stimulating the body’s immune defenses using immunotherapy.We recently discovered three types of RRD-gliomas (RRD1-3). Each type acts differently and responds to treatment in its own way. We believe using specific treatments for each group will help patients live longer with fewer side effects. Our plans are:RRD1: These tumors have many immune cells. We will reduce use of harmful treatments like radiation.RRD2: These tumors have fewer immune cells. We will use two kinds of immunotherapy together to help the body fight the cancer.RRD3: These tumors have little immune activity. We will use immunotherapy with drugs that target special features of the tumor. These ideas are based on strong lab studies, tests in animals, and early results in patients. Now we will study how each tumor type responds differently to more precise treatments. We will track and adjust this in real time by testing tumor DNA in the fluid around the brain and spine. This project will advance research and improve care for young people with these deadly brain tumors. In the future, it will be expanded to help treat other types of deadly cancers.

Augusto Faria Andrade, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Some brain tumours in children grow very quickly and are hard to treat. As a result, many children affected by these tumours have poor outcomes. Scientists know that changes in the DNA of tumour cells help them grow, but they are still learning how these tumour cells interact with the body’s immune system. Tumour cells are surrounded by immune cells, which can sometimes help the body fight the cancer, but in other cases, they may help the tumour grow. Researchers have worked for years to help the immune system find and kill cancer cells. While this approach has worked well for some types of cancer, it has not been effective in treating paediatric brain tumours. By studying the tumour and immune cells together, we hope to identify which types of immune cells are present, what they do, and how they interact with brain and tumour cells. Our study aims to learn how immune cells act around these tumours and how we might be able to change their behaviour to help fight the cancer. We will test whether blocking specific cell communications can help slow down tumour growth and train the immune system to recognise and attack the cancer. What we learn here could lead to new treatments that help children with these serious brain tumours live longer and healthier lives.

Siyuan Liu, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Diffuse midline glioma is a deadly brain tumor that affects children. Radiation is the main treatment, since surgery and chemotherapy do not work well. New drugs are being tested, but they are not proven yet. To find better options, we built a new method that combines gene disruption with detailed study of brain tumors. This lets us test the role of many genes in new ways. We found genes that may help tumors respond better to treatment. Now, we will study how these genes work. Our goal is to discover new treatment combinations that can help children with glioma live longer and healthier lives.

Lillian Guenther, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

My group investigates specific features of pediatric bone tumors that allow them to survive. One cancer we are interested in is Ewing sarcoma. Ewing sarcoma is a common bone tumor in children. It is challenging to treat, particularly when the cancer has spread. We have become interested in a protein that is important for Ewing sarcoma cells. We want to understand what this protein does in cells. This will help us to kill Ewing sarcoma cells. We are also working with chemists to make new drugs to disrupt its activity. We will test these in Ewing sarcoma cells. Our hope is that these studies will eventually lead to new treatments for Ewing sarcoma.

Toshiro Hara, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Brain cancer is an unwelcome guest that sneaks into a kid’s brain. Doctors can usually see and take out the cancer, but it gets really difficult when the cancer enters normal brain areas. This sneaky move by cancer is called invasion. The problem is that these cancer cells are so small and tricky that even our best medical scanners can’t find them. It is like the cancer is playing a game of hide-and-seek in the kid’s brain and escaping from the doctor’s tools.We know some of the places the cancer hides, but we don’t understand why it chooses certain paths or how it moves so easily. So, what we did was take a super close-up look at how brain cancer behaves using a special research tool. This is a way to see exactly what is going on inside individual cancer cells. Our first look tells us that brain cancers are like masters of disguise — they can look like normal brain cells, especially when they are hiding among them, and it seems they might even be “talking” to the normal cells around them.We will dive deep into how these cancer cells chat with healthy brain cells and what special tools or genes they use to travel so well. We believe figuring this out could put the brakes on cancer’s sneaky move. It could lead to new treatments that stop their play and talk, making treatment much more effective and helping many kids.

Christina Von Roemeling, PhD

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.

Martina Damo, PhD

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.

Stefanie Bailey, PhD

Funded by the Bakewell Foundation

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.

Prerna Malaney, PhD

Colorectal cancer (CRC) is frequently diagnosed when it has already spread to other parts of the body. When caught early, 65% of patients survive for five years, but if the cancer has spread, only 12% survive that long. This makes it critical to understand what causes CRC to spread and find better ways to treat it. Cancer spreads when certain genes become more or less active. Scientists have mostly studied how genes are turned on and off, but recent research shows that another process, called post-transcriptional regulation, is also important. This refers to all the steps that happen between when a gene is copied into RNA to when it is turned into a protein. These steps, such as modifying, transporting, or breaking down RNA, add another layer of control over how much of a protein a cell makes. RNA-binding proteins (RBPs) help manage this process. But when RBPs don’t work properly, cancer cells may grow and spread more easily. We will use a genetic screening method to find all RBPs that play a role in cancer spread. By studying these proteins, we hope to better understand how CRC spreads and discover new ways to stop it.

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