Grant Archive - Page 3 of 141

Tikvah Hayes, PhD

Funded by the Stuart Scott Memorial Cancer Research Fund

Lung cancer is the leading cause of cancer-related deaths worldwide. The most common type is called non-small cell lung cancer (NSCLC), which consists mostly of adenocarcinomas and squamous cell carcinomas. In about 15–20% of adenocarcinoma cases, the cancer is caused by changes in a gene called EGFR. This gene normally makes a protein that helps cells grow and divide in a healthy way. But when EGFR is changed, or mutated, it can send the wrong signals, causing cells to grow out of control and form cancers. There are already drugs that target some EGFR mutations. These medicines, called EGFR tyrosine kinase inhibitors, can be very effective for certain patients. However, they only work for specific mutations in one part of the EGFR protein. Other mutations, found in a different part of the protein called the extracellular domain (the section that sits outside the cell), don’t respond to any of the current treatments. These mutations are less common, but they still affect many people with lung cancer. Unfortunately, scientists know far less about them. Our project aims to change that. Using human lung cells and advanced 3D models called organoids, we are studying how these rare EGFR mutations cause cancer, how they interact with other cancer genes, and why today’s drugs don’t work. We are also using new genetic tools to search for weak spots in these cancer cells that could become targets for future medicines. By uncovering how these overlooked mutations drive cancer, we hope to open the door to better treatments for patients with lung cancer.

Jared Rowe, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Neuroblastoma is the most common cancer in babies. It can act in surprising ways. Some forms grow quickly and are very hard to treat. Others, especially in babies under 18 months old, can shrink or even disappear without treatment. Doctors do not fully understand why this happens, but the immune system may play a key role. One type of immune cell, called the CD8⁺ T cell, is especially good at finding and killing cancer cells.This project will study whether the immune system in babies works differently from that of older children or adults, and whether these differences can explain why some tumors go away on their own. Baby T cells are often thought of as immature, but new research shows they can grow faster, work more efficiently, and resist “burning out” better than adult T cells.In our early work, we trained baby T cells to recognize neuroblastoma cells. They were better at killing these cancer cells than adult T cells. We also found that baby T cells rely on a nutrient called pyruvate for energy and function. They process pyruvate in a special way using an enzyme called GPT.We will test whether this unique metabolism is the reason for their strong performance. We will also see how the tumor environment changes T cell metabolism, and whether changing the way T cells use pyruvate can make them even better at fighting cancer.We will use umbilical cord blood as a safe, widely available source of baby T cells. If this approach works, it could lead to new cancer treatments designed for children. The goal is to make these treatments safer, more effective, and take advantage of the natural strengths of the infant immune system.

Craig Byersdorfer, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Treatment of childhood cancers is tough. However, our recent success rate has improved. This is because of our ability to redirect the immune system to attack cancer cells. These advances have resulted in many cures. However, success has not been perfect. Relapses continue. Further, we know the risk of cancer increases when immune cells go away. Or when the cells do not function properly. It has also become clear that knowing the energy pathways used by immune cells is vital. This knowledge can help predict how well our treatment will work. However, it has been challenging to reprogram immune cells. Many treatments restrict cell growth. Or limit cell number. In our studies, we discovered a new way to reprogram cancer-targeting immune cells. Our method improves their anti-cancer properties. Without limiting cell growth. Or function. We believe that these beneficial changes will increase the chance of a successful treatment. Especially when immune cells are given back to children with high-risk leukemia. In the current application, we will test our new treatment in many ways. We will test immune cells recovered from leukemia patients. We will compare our approach to similar treatment strategies. We will define whether immune cells need to stick around. And, we will extend our studies into ‘real world scenarios’. Together, we hope to bring our treatment to patients with high-risk leukemia. Within the next five years.

Hanna Mikkola, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Children with Down syndrome have a higher chance of getting blood cancer called leukemia. Many babies are born with a condition called transient abnormal myelopoiesis (TAM). TAM starts before birth and causes too many immature blood cells to grow. In most babies, TAM goes away on its own. But in some, it can be very serious or later turn into leukemia. Right now, doctors do not know why this happens or how to tell which babies are at risk.In this study, we will use new tools to look at single blood cells to learn more about how TAM starts, how it changes into leukemia, and why treatments sometimes stop working. We will study blood and bone marrow samples from children at different stages of the disease, as well as from pregnancies with Down syndrome, to find out when and where the first changes begin.Our goal is to find better ways to predict which babies with Down syndrome will get leukemia and to develop safer, more effective treatments. This work could improve survival and quality of life for children with Down syndrome and their families.

Raymond Moellering, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Burkett’s lymphoma and neuroblastoma are two different types of childhood cancers that share a common link: the MYC gene. Chemotherapy is often used for treatment, but the side effects can be hard on young patients. Doctors and researchers now know that the side effects are mostly from blocking the growth of both cancer cells and healthy cells. Chemotherapy also does not work well for some patients. Our research focuses on drugs that target MYC to safely slow the growth of cancer cells. We will test these new drugs in the laboratory for future development into medications for patients. In the end, our work will produce better medicines to treat these cancers without giving up patient comfort.

Chrysothemis Brown, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Cancer immunotherapy is a treatment that helps the body’s immune system fight cancer. It works very well for some cancers, but it is less effective in infants and children. One reason is that the young immune system is built to turn down strong reactions. This helps babies avoid harmful inflammation when they first eat food or meet the friendly bacteria in their gut. The Brown Lab recently found a new type of immune cell, called Thetis cells. These cells play an important role in suppressing immune responses during early life. We think they may also train the immune system not to attack cancers, which lets tumors grow. In this project, we will study how Thetis cells act in childhood cancers such as hepatoblastoma and use what we learn to design new treatments.

Uri Tabori, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

When the body is unable to fix damaged DNA, it can cause some childhood cancers to grow very quickly. These cancers have many DNA changes (called “mutations”) so we call them “hypermutant”. Some children are born with a syndrome, called CMMRD, which makes them develop a lot of these hypermutant cancers at a young age. A treatment called immunotherapy has shown positive results in these patients. However, it doesn’t work for everybody and when a cancer is found late, about 40% of children will get worse, even after treatment. Immunotherapy can also cause side effects, some of which are serious. Recently, we discovered that mRNA-LNP vaccines (similar to those used for COVID-19) may actually be able to prevent cancers in children with CMMRD. These vaccines have very few side effects and might help many patients. However, we still need to learn more about what components make an effective vaccine and then test it in human and animal models. In this project, we will do three things. We will first determine what should be included in a vaccine to make it work well. We will then test the vaccine in mice to see if it can prevent cancer. Finally, we will see how well the vaccine works and how safe it is for humans. To do this, we will work with international collaborators who have experience making vaccines. This work has the potential to help children with many other cancer-causing syndromes, as well as common adult cancers.

William Gwin III, MD

Funded by the Cancer Vaccine Coalition (CVC)

Over 310,000 people get breast cancer each year in the US. About 20% of breast cancers are caused by a protein called HER2 and are aggressive. We have developed a vaccine called WOKVAC that trains the immune system to identify and kill cancer cells that have high levels of HER2. Early results in patients show that the vaccine is safe and can create a cancer-killing immune system response. We are now conducting a patient trial where patients with HER2+ breast cancer get the vaccine along with their normal treatment before they have surgery to remove the tumor. Our goal is to have the vaccine create cancer-killing immune cells that will work together with their normal treatment to kill the cancer cells and protect the patient from the cancer for years or decades. So far, we have given the vaccine to 16 patients on this trial. The vaccine has been safe, and early results are encouraging. We are expanding the trial to 25 patients to better help us decide if other patients should get this vaccine. We are looking at how well the patients do after getting the vaccine and looking to see if the vaccine increases the number of cancer-killing cells in their tumors and blood.

Reshma Mahtani, DO

Funded by Hooters

This project is about helping young women, age 45 and under, who are diagnosed with breast cancer. These women often have more serious types of cancer and are diagnosed later than older women. We want to make it easier for them to learn about and join clinical trials. Clinical trials are studies that test new treatments to see if they work better than current ones.We want young women with breast cancer to get clear information and strong support when making choices about their care. Many are also dealing with big life events like having children, starting careers, or handling stress. These things can make it hard to think about joining a clinical trial. By adding a research assistant and training nurses to help, we hope to make the process easier and less confusing.This program will help young women feel more confident and informed about their treatment options. It will also help them learn about new therapies through clinical trials. By giving support and easy-to-read materials in both English and Spanish, we hope to improve their care and make their experience less stressful.

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.