Funded by the Dick Vitale Pediatric Cancer Research Fund
Osteosarcoma (OSA) is a bone cancer that mostly affects young people. Surgery and chemotherapy are the most common forms of treatment but can cause serious side-effects that make patients very ill. When a patient’s OSA has spread from the bone to the lungs it is much harder to treat. Recent research has shown that immune cells can be engineered to improve their ability to fight cancer. This approach has cured patients with certain blood cancers when all other previous therapies failed. However, this approach is less effective in “solid” cancers like OSA. We are pursuing a new approach where immune cells that naturally recognize mutated proteins in a patient’s tumor (TIL) are collected and grown to large numbers before returning them to the patient. This approach has achieved cures in several solid cancers, including those that have spread to other areas of the body including the lungs, but it is not always effective. In previous work, we found that disabling a gene called CISH allows TIL to kill cancer cells more effectively. We are currently testing this in a clinical trial in patients with gastrointestinal cancer. In the current proposal, our goal is to see if this approach can also be used to treat OSA. If successful, our approach may offer a curative option with far fewer side-effects compared to current therapies.
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.
This new drug, called peptide alarm therapy (PAT), is injected directly into a tumor to stimulate immune cells to attack the tumor. This drug stimulates immune responses that people already have because of exposure to viral infections and/or vaccines. We found that, in mice, injection of this drug in combination with a PD-L1 inhibitor, a drug already approved by the FDA, eliminates tumors. This new drug can be used for different types of solid tumors and is expected to have few side effects. This is a first clinical trial of this new type of drug to determine if it is safe. This new type of drug may be effective against many different tumor types in adult or pediatric patients.
Abeloff V Scholar * (Tie for Top Rank)
Cancers of the brain and spine are hard to cure and are often lethal. Knowing if and when a cancer will recur has been challenging to predict. We do not have a good test to determine which cancers will return quickly and which will not. For this reason, nearly all patients are given the same treatment that often involves surgery, radiation, and drug therapy.
A holy grail in cancer research is to create a test that can predict cancer behavior. Our laboratory studies DNA structure and how it can be used to predict cancer behavior. One goal of our laboratory is to create a test based on DNA structure that can pick out the aggressive brain cancers from the less aggressive ones. A second goal is to create a test that can tell which cancers might respond to new drug treatments. To do this, we use a combination of cutting-edge experimental and computational approaches. We anticipate that such research will lead to the ability to create a treatment plan for each patient individually. We can treat aggressive cancers with tailored plans, whereas we can hold on treatments for cancers that are unlikely to need it.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND
Ovarian cancer is a deadly disease. A goal of ovarian cancer treatment is to find drugs that allow patients to live longer. The methods that predict whether these drugs work ignore proteins. There is no information about how proteins affect survival. Also, it is not known how proteins contribute to harmful side effects. In this project, we will identify the proteins that are involved in responding to a group of drugs named PARP inhibitors. These drugs are used to treat patients with the most deadly form of ovarian cancer. It is critical to identify the proteins associated with good PARP inhibitor response. This will help us to understand how PARP inhibitors have anti-cancer activity. As a result, it will be easier to identify the ovarian cancer patients who will respond to PARP inhibitor treatment. This research project supports the goal of the V Foundation, and it will help to accelerate victory over ovarian cancer.
Funded by the 2019 Wine Celebration Fund a Need for Canine Comparative Oncology
Sarcomas are malignant cancers that form in bone and soft tissues (muscle, cartilage, nerves) in many species. Sarcomas are rare and often affect children and teenagers. Outcomes have not changed much in the last 10 years. New treatments are needed to better cure these tumors. Because sarcomas are not common in people, it can be hard to test new treatments. Pet dogs commonly develop sarcomas, and their tumors behave like human tumors. Pet dogs with sarcoma give us a chance to test new treatments that can help both dogs and people. Radiation therapy is commonly used to kill sarcoma cells in dogs and humans but it cannot cure tumors by itself. Radiation therapy can also cause an anti-cancer immune response, where the body’s own immune cells kill tumor cells for a short time. In this study, we are exploring a new way to use the immune system to work with radiation therapy to destroy sarcoma cells. We have invented a designer drug specifically for dogs that “kick-starts” the anti-cancer immune response. We expect that this drug will help us improve outcomes for patients with sarcomas when radiation therapy is used. We will test this expectation in the laboratory and in pet dogs with sarcomas that need treatment. This project will help us learn to use a drug like this in people with sarcomas that need radiation therapy.
Funded by the Dick Vitale Gala
Sarcomas are cancers of bone and connective tissue. These cancers are not very common in people, but they are no less serious than other, more common cancers. One reason there are few new treatments for sarcoma is that their rarity makes it difficult to obtain material for study. To overcome this, we have studied sarcomas in animals, and especially in pet dogs. Dogs share our environment and their risk to develop cancer is about the same as it is for humans. But unlike people, dogs develop sarcomas very commonly. Over the past twenty years, we have found how sarcomas of dogs are like sarcomas of people. This creates opportunities to develop new sarcoma treatments in dog “patients”. For this project, we are studying how we can activate the immune system to kill sarcomas – and specifically bone cancer. Our strategy starts with a virus that infects and kills cancer cells. Because this allows the immune system to recognize the tumor, we can then add a protein to enhance the potency and duration of this immune response. The idea is that the treatment will eliminate the primary tumors and prevent or delay cancerous spread to other organs. We will test our strategy in the laboratory and in dogs with bone cancer in a clinically realistic setting, which will provide avenues to move our findings more quickly to human patients who will ultimately benefit from this therapy.
Funded by Papa John’s International
Funded by the Dick Vitale Gala in honor of Leah Still
Neuroblastoma, an embryonal tumor that arises in the peripheral sympathetic nervous system (PSNS), accounts for ~10% of cancer-related deaths in childhood. About half of all patients, especially those over 18 months of age with amplified copies of the MYCN oncogene, present with evidence of widespread metastasis at diagnosis and have a very high risk of treatment failure and death despite receiving greatly intensified chemotherapy. Attempts to improve the treatment of metastatic neuroblastoma have been slowed by the lack of a full understanding of the multistep cellular and molecular pathogenesis of this complex tumor. Recently, I developed the first zebrafish model of neuroblastoma metastasis by overexpressing two oncogenes, human MYCN, which is amplified in 20% of neuroblastoma cases, and mutationally activated SHP2, which is the second most frequently mutated gene in high-risk neuroblastoma. This transgenic model affords unique opportunities to study the molecular basis of neuroblastoma metastasis in vivo, and to identify novel genes and pathways that cooperate with MYCN and activated SHP2 to promote this usually fatal stage of disease development. This research approach is expected to reveal novel molecular targets that can be exploited therapeutically. To achieve this goal, I propose to establish reliable in vivo zebrafish models of the aberrant genes and pathways that contribute to neuroblastoma metastasis. In the near future, these models will be used to screen for effective small molecule inhibitors that block specific steps in metastasis with only minimal toxicity to normal tissues, and thus would be assigned high priority as candidate therapeutic agents.