Valentina Hoyos, MD

Funded by Hooters of America, LLC

Breast cancer is the most common type of cancer in women, causing many deaths each year. When the cancer has spread in the person’s body, the available treatments have many side effects and often cannot cure the disease. Research has shown promising results using immunotherapies, which make the patient’s own immune system attack the cancer. T cells are important cells of the immune system and can be very effective at attacking and killing cancer cells. Some breast cancers have a protein called HER2 that can be used as a target for T cells to attach. We plan to take the patient’s own T-cells and train them in the laboratory to attack breast cancer cells that have HER2. This treatment has proven safe in other cancer types and should have minimal side effects. However, breast cancer tumors are made up of different kinds of cells, not just cancer cells. Thus, we also plan to arm the T-cells with extra measures to get rid of the other bad cells in the tumor, making it easier for the T cells to eliminate all of the cancer. Based on previous research, we know that when successful, results using this kind of T cell-based therapy are long lasting for patients and can even cure their disease. With the recent FDA approval of T-cell therapies for several cancers, we are confident that the proposed project has the potential to improve the lives of patients with breast cancer.  

Gregory Friedman, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Outcomes for children with brain cancer are poor and current therapies are harmful to normal cells in the body. New therapies that only target cancer cells are greatly needed to improve outcomes for this terrible disease. We tested the ability of a modified cold-sore virus to target and kill brain cancer while not injuring normal cells in children. Results from the clinical trial were very exciting. We found that the virus directly kills cancer cells and also stimulates a child’s own immune system to attack the tumor. From the trial, we learned that in order to achieve even greater responses from the therapy, we need to continue the immune system attack on the tumor. To achieve this goal, we will combine two therapies that work well together: the altered cold-sore virus with a unique cancer vaccine. When the cancer vaccine is given before the virus, it prepares the immune system to fight the cancer and improves the virus’ ability to kill the cancer and stimulate the immune system attack on the cancer. We plan to create the ideal cancer vaccine with the cold-sore virus in the lab and then conduct a clinical trial of the combination therapy to benefit children in great need of more effective and less-toxic treatments. We expect these exciting therapies will result in even better outcomes in children with brain cancer. Importantly, this combination therapy can be used to treat other pediatric cancers, increasing the overall potential to help children with cancer and their families. 

Michael Evans, PhD

Funded by the Constellation Gold Network Distributors

Although cancer immunotherapies are beneficial for many patients, about half of patients fail to respond to treatment or may only respond for a short time.  Identifying which patients are benefitting from treatment is an important goal, as non-responders are subjected to needless treatment and deprived of potentially beneficial alternative therapies.  To address this challenge, we have developed a new PET scan to identify which patients are experiencing a tumor remission rapidly after the start of treatment.  We will first evaluate patients with non-Hodgkin’s lymphoma that are receiving CAR T cell therapy.  If our imaging technology successfully identifies patients that are responding to treatment, we expect it could also help patients with other types of cancer that are receiving immunotherapies.  Another long term goal will be to test if our imaging technology can help physicians understand if new immunotherapies in clinical trials can eliminate tumors. 

Jaehyuk Choi, MD, PhD

Merkel cell carcinoma (MCCs) is a cancer that requires additional research. It is the most deadly skin cancer. Moreover, its incidence is rising, doubling from 2000 to 2013. Until recently, there have been no effective therapies for this disease. Immunotherapies have revolutionized the treatment of MCCs. Roughly 50% of patients respond to these treatments, called PD1 inhibitors. While this is an important advance, there are critical barriers to cure. There are no biomarkers to predict who will respond to treatment. Moreover, there are no treatments for patients who fail immunotherapy. To address this critical unmet need, we have assembled a large clinical cohort of patients with MCCs across multiple institutions. We will subject them to a number of assays designed to identify what immune cells are in each sample and what they are doing. Our goal is to identify patterns that predict who responds to therapy and why or why not. The biomarkers we discover can be immediately deployed to ensure that PD1 inhibitors are only given to patients likely to respond to them. For the rest, our studies will seek to identify novel immunotherapy drug targets. If successful, we can develop new drugs that can be used against these novel targets and test them in future clinical trials. This knowledge will be critical to improve patient care and a key advance to developing a cure for this deadly disease. 

Alison Taylor, PhD

Funded by the Constellation Gold Network Distributors

Genetic information is carried in DNA, which is present in every cell of our bodies. Most cells have 46 chromosomes, which carry DNA within the cell. However, more than 90% of tumors have cells without the correct number of chromosomes. These cells are called “aneuploid”. Some whole chromosomes or large chromosome fragments may be duplicated or lost. Aneuploidy is a contributing factor in cancer formation. However, its exact role in this process is an unanswered question in cancer biology. The goal of this research is to understand the effects of different changes in chromosome number.  

For our studies, we make use of a new technology that allows us to cut chromosomes at specific locations. With these experiments, we can study the effects of changes in large chromosome segments. Our current focus is a type of cancer called squamous cell carcinoma (SCC). In this cancer type, large pieces of chromosome 3 are affected. Here, we will uncover the interaction between chromosome 3 changes and DNA mutations. We will also create a human cell model of SCC. These studies address a gap in our understanding of aneuploidy in cancer by studying the effects of specific sets of chromosomal changes. With knowledge of how these chromosomal changes contribute to cancer formation, we will uncover new ways that cells can become cancerous. A better understanding of paths to disease formation will be crucial for designing new cancer treatments. 

Christopher Seet, MD PhD

Harnessing the immune system to eliminate tumor cells has led to remarkable responses in several advanced cancer types. T cells are the key immune cell type which are engineered in the lab to seek out and destroy tumor cells, however in many cases tumor cells adapt to evade T cell killing, leading to disease relapses. Advances in cell engineering now permit T cells to be made in the lab from specialized stem cells. This technology promises to provide more cancer patients access to T cell therapies, but also presents the opportunity to make T cells more effective in prevent tumor escape. The goal of this research project is to study the ways in which tumor cells evade killing by lab-grown T cells, and how engineering specific molecules on lab-grown T cells may enable us to turn on tumor killing mechanisms to prevent tumor cell escape. Our overall goal is to further the development of this new kind of T cell therapy to be more effective across a wider range of cancer patients. 

Siddhartha Mitra, PhD

Funded by the Constellation Gold Network Distributors in honor of the Dick Vitale Pediatric Cancer Research Fund

Brain cancers have recently surpassed blood cancers as the most common cause of cancer-related death in children. The big question we ask here is how we can make cancers easy to destroy from the inside by the body’s own soldiers. Modern cancer-treating drugs utilize the body’s defense mechanism to destroy tumors and have shown promising results against several cancers. However, most of these drugs have been developed against adult tumors and do not always behave similarly against childhood cancers. Furthermore, a lack of suitable targets that can differentiate childhood brain cancers from normal cells prevents the safe treatment of childhood cancers. This is more so due to our lack of understanding by which cancer cells hide from the body’s soldiers, especially in brain cancer.  While significant progress has been made in the care of children with medulloblastoma, some of those patients still suffer a lot. The cells create a signal on their surface which identifies healthy cells from diseased cells. It tells a particular type of cell called macrophages not to eat these cells. Macro meaning big and phages meaning eater mean Big Eater. The body uses some proteins to protect cells that should remain and help dispose of diseased cells. Cancers use this to create a force field to protect themselves. In this grant we will test how to reduce this force field on the surface so we can use the bodies soldiers to eat up the tumor. 

Margaret Callahan, MD, PhD

Funded by the Stuart Scott Memorial Cancer Research Fund in memory of James Ebron *

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Immune checkpoint blockade (ICB) is one type of immunotherapy that has been FDA-approved for the treatment of melanoma, bladder cancer, lung cancer, and other cancers. For some patients, ICB can lead to dramatic shrinkage of their tumors and extend their life. However, many patients do not see this benefit and some patients develop serious side effects. For most cancer patients, there is no way to predict if they will benefit from or be hurt by ICB. A test that could give doctors and patients a better understanding of the risks and benefits for ICB treatment for each individual is urgently needed. Examining the blood of patients, we discovered certain immune cells in patients who are less likely to benefit from ICB. We have found this is true for both melanoma and bladder cancer patients. We plan to examine whether these cells also matter for patients with other cancers and if there are differences in these immune cells depending upon a patient’s race. We also would like to better understand this special population of immune cells and how they may be linked to immune cells in the tumor. We hope that this will lead to the development of a safe and easy test that will provide patients better information about how ICB treatment will work for them. With this information, we hope to allow patients to feel and function better and live longer by finding a therapy that will be more likely to help and less likely to hurt them. 

Liling Wan, PhD

Acute myeloid leukemia is the deadliest blood cancer. The mainstay chemotherapeutic treatments have met with limited success, and most patients will die from their disease. Thus, New treatments are desperately needed. To address this need, we have identified a cellular pathway leukemia cells rely on to live. In this project, we have developed an inhibitor that blocks this pathway and found that it kills leukemia grown in mice. We would like to understand why some leukemia cells rely on this pathway to survive and what determines the response to the inhibitor. If successful, our work will provide preclinical evidence for a new pathway as a target for acute myeloid leukemia and offer needed knowledge and chemical tools to guide future clinical studies. We are hopeful that our findings could lead to improvements in the lives of AML patients.  

Anastasia Tikhonova, PhD

Immunotherapy is a type of cancer treatment that uses the body’s own immune system to fight and destroy cancer cellsDespite its success in treating a number of cancers, immunotherapy has had a limited impact on the treatment of blood cancers, known as leukemia. While there are many reasons for this, a primary reason is the current lack of understanding of how the cells of the immune system interact with leukemia cells. Present knowledge of the types of immune cells that live in the bone marrow and their behavior at various stages of leukemia are almost entirely lacking. To address this, we will perform a widespread analysis of immune cell composition and function during leukemia disease progression. We will use cutting-edge technology to understand the biological mechanisms that become altered during leukemia, which may cause immune cells to promote the cancer’s initiation and relapse. These studies would enable the identification of “immune signatures” associated with different stages of cancer developmentThe findings will lay the groundwork for our understanding of the bone marrow immune landscape in the context of the human disease. We envision that these studies will fundamentally lead to new treatment strategies for this devastating cancer and thereby improve patient outcomes.  

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