Parker Bridge Fellows Program; Funded in partnership between Parker Institute for Cancer Immunotherapy and the V Foundation
Cancers are driven by mutations, or changes in the DNA that encode the proteins and processes that allow the cells in our body to function normally. Those mutations make proteins work differently, making cancer cells grow faster or live longer, but they also make cancer cells look different from normal cells to the immune system. This process is similar to when someone gets a viral infection, where viruses infect normal cells, and the immune system battles the infection by recognizing the infected cells by the presence of viral proteins.
There are a series of molecules, called the Human Leukocyte Antigens (HLAs), that are responsible for showing those foreign proteins to the immune system on the surface of the diseased cells. Cancer cells can also change or lose these HLAs, so that the immune system no longer sees the cancer cells as “different” from normal cells. My research is focused in understanding these HLA molecules in skin cancer, to address the question of how the cancer cells avoid getting killed by the immune system. Skin cancers are generally treated with therapies that help the immune system kill cancer cells, and my research helps us understand why these therapies may or may not work. By explaining whether HLAs are different in cancer cells, my research may improve the success of our treatment strategies in skin cancer.
North Carolina (NC) has the largest American Indian population east of the Mississippi River. Yet, we do not know much about the health and health care of NC American Indians. Because cancer is the number one cause of death in NC American Indians, we need to better understand cancer and cancer-related needs in this unique population in order to reduce the cancer burden. Three NC cancer centers joined together in 2021 to partner and learn more about how to help American Indians with cancer. We also want to find and develop community resources for American Indians with cancer in North Carolina.
In this study, we will explore how cancer affects American Indians in North Carolina. First, we will measure the number of cancer diagnoses and deaths from 2003-2019. We will also learn more about how and where American Indians receive cancer care. These data will come from the North Carolina Cancer Registry and health insurance files. Second, we will ask tribal leaders to help us explore the needs and barriers to healthcare in American Indian communities. Finally, we will work with American Indian youth leaders to understand tribal community strengths and local resources that can help with cancer care.
This information will help American Indians by showing where the greatest needs lie and pointing to opportunities for better care, with a long-term goal of improving cancer outcomes in all American Indians.
Funded in Collaboration with the University of Florida Foundation
Brain cancer is now the leading cause of cancer-related death in children, due to the significant improvements in outcomes for children with more common cancers such as leukemia. This research proposal advances a novel immunotherapy treatment for medulloblastoma (MB), the most common malignant brain tumor in children. We have pioneered a treatment platform for pediatric brain tumors called adoptive cellular immunotherapy, which involves expanding tumor-reactive ‘killer T cells’ to large numbers outside of a patient and delivering these potent immune cells back to children with resistant brain tumors. This approach is currently undergoing evaluation in first-in-human clinical trials at our center. This project will advance this platform into a next generation approach that uses genomic technology to identify patient-specific antigens expressed in medulloblastoma tumors and specifically isolate and expand T cells recognizing these unique tumor targets (called neoantigens). If the objectives of this study are met, we will be able to significantly enhance the specificity and potency of an already promising platform and rapidly translate our findings into innovative clinical trials for children battling brain cancer.
Funded in partnership with WWE in honor of Connor’s Cure
Brain tumors are the largest cause of cancer-related death in children. A subgroup of brain tumors known as DMG are the deadliest type, with most children dying within two years of their diagnosis. The location of these tumors makes surgery difficult and there is a need for effective therapies. One hallmark of DMGs is de-regulated (meaning too much or too little) epigenetics. DNA is a language in each of us that translates a set of instructions, determining features like our eye and hair color. Epigenetics provides the structure that allows cells to decode the DNA instructions for proper function. Patients with DMG have changes that result in faulty instructions that make cancer cells grow faster or migrate to other parts of the brain and body. A second emerging hallmark of DMGs is distorted metabolism, which is the chemical reactions in the body’s cells that change food into energy. We have made the discovery that brain tumor epigenetics is highly dependent and linked on certain nutrients. These nutrient sources help brain tumor cells to hijack epigenetic reactions to promote growth. By reducing the fuel that the cancer cells rely on, we aim to kill brain tumor cells while leaving normal cells unharmed. Why is this important? Pediatric brain tumor research has not generated sufficient advances and this proposal aims to help address that.
Parker Bridge Fellows Program; Funded in partnership between Parker Institute for Cancer Immunotherapy and the V Foundation
Cancer immunotherapy holds great promise to treat cancers since it boosts the human body’s own immune system to eradicate cancers. Cytotoxic T cells are the central arsenal in our immune system to find and attack cancer cells without harming the healthy cells. These T cells harbor a high diversity of T cell receptors (TCR) to specifically recognize tumor neoantigens, which are proteins arising from mutations in cancers but not in normal cells. Neoantigens are highly unique in each patient. Therefore, it is essential to identify tumor neoantigens and paired TCRs in each patient to develop personalized cancer immunotherapies such as tumor neoantigen vaccines and TCR-engineered T cell adoptive therapy. Here we will develop an innovative platform to map neoantigen specificity, TCR repertoire and molecular phenotype of T cells at the single-cell level. This platform will permit a rapid, low-cost, and high-throughput mapping of patient-specific neoantigens, allowing cancer immunotherapy more accessible to each patient. Linking TCR recognition of tumor neoantigens with molecular programming of tumor-targeting T cells, we will understand how the T cells “see” neoantigens impact their cell fate decision to become highly-protective T cells that eliminate cancers or exhausted T cells that cannot work. Completion of this work will significantly facilitate the development of patient-tailored cancer immunotherapy.
Funded by 2021 Kay Yow Cancer Fund Final Four Research Award
Black Americans (BA) with triple negative breast cancer (TNBC) have more aggressive disease and worse outcomes compared to Caucasian Americans. The goal of this project is to test if a novel immunotherapy will be effective in treating triple negative breast cancer in BA using preclinical models. We have generated two immunotherapy drugs that use a type of immune cells in the body called natural killer (NK) cells. NK cells normally function to kill cells and fight viral infections in our body. The drugs we have made train NK cells to recognize and find cancer cells that have two markers that are present on cancer cells from BA patients with TNBC. Once the NK cells find these cancer cells, they will eliminate them. We will test if these drugs kill cancer cells in models that are developed from BA patients with TNBC. The results of this proposal may show that NK-cell-based therapy could provide a new treatment option for BA TNBC patients and reduce their mortality from this disease.
Parker Bridge Fellows Program; Funded in partnership between Parker Institute for Cancer Immunotherapy and the V Foundation
Using the immune system to fight cancer is an exciting area of research that has led to cures for some cancers that could never be cured before. These “immune therapies” teach and enable cells in the immune system to recognize and fight cancers. Unfortunately, making effective immune therapies is difficult for deadly cancers of the brain. One challenge is that immune cells are not able to get into the brain as easily as other parts of the body. Another challenge is that the cells in the tumor can suppress the immune system, so that even when immune cells enter the brain, they cannot kill the tumor. We are interested in studying how cells interact inside of tumors to better understand why some immune cells are effective at killing tumors and others are not. My research uses a new kind of microscope imaging to see tumor cells and immune cells with more detail than ever possible before. This allows our lab to look at the structure of brain tumors to better understand how immune cells enter the brain and interact with other cells in the tumor. By understanding better how brain tumors and immune system influence each other, we hope to make more effective immune therapies to treat this deadly type of cancer.
Lineberger Comprehensive Cancer Center (LCCC) is committed to making cancer care accessible to the people of North Carolina. This includes opportunities to participate in clinical trials, which are important to improving cancer treatments. Few patients participate in clinical trials, and fewer still are patients who identify as Black, Indigenous, or a person of color (BIPOC). Many BIPOC patients are hesitant to participate in clinical trials. Enhancing diversity in our workforce will help BIPOC patients feel more comfortable enrolling in trials. This grant will provide opportunities for local BIPOC college students to learn about cancer care and research. The goal is to create interest in pursuing a career in this field at LCCC, and ultimately, ease hesitations that prevent BIPOC patients from participating in clinical trials. We will partner with NC Central University in creating a summer internship for 5 students. Students will be matched with mentors with experience in cancer research, clinical trials, and patient care. Students will also receive overall professional development such as resume and presentation development. To measure project success, we will encourage students to provide feedback during and after the program. A follow up survey will allow students to provide additional insights such as barriers to participation and measure their interest in a cancer related field. We will follow the students over time to understand the number that become employees at LCCC; we will also measure the number of BIPOC patients who enroll on clinical trials at LCCC.
Parker Bridge Fellows Program; Funded in partnership between Parker Institute for Cancer Immunotherapy and the V Foundation
Cancer remains the second leading cause of death in the US. In order to tackle cancers, a new kind of therapy has emerged, termed immunotherapy, which aims to boost the immune system’s ability to fight the cancer. However, a major fraction of patients do not respond to immunotherapies currently. If we can figure out what other roadblocks to the immune system exist in these patients, we could expand the benefits to survival and quality of life to more people.
The immune system is a complicated team, with different cell types doing different roles. In order to work together these cells must talk to each through cell signaling and have to be in the right formations to carry out a successful play against the tumor. We want to discover how this teamwork can break down and design therapies to patch those issues.
The tumor is made up of more than just immune cells of course, and our project will focus on two types of cells that talk to the immune system. One cell type is the fibroblast which makes the building materials that hold our tissues together. Another cell type is the endothelial cell which forms blood vessels which serve as the roads and highways that carry cells, nutrients, and drugs into the tumor. If we can understand how these cells break immune cell teamwork, we can reveal new weak spots to target, making immunotherapies even stronger.
