Great strides have been made toward finding cures for cancer, which is expected to strike 1.6 million Americans this year. Although many cancer patients still die from their disease, the overall cancer death rate is declining due to improved detection methods and novel therapies. The exciting development of immune therapy has shown that activating a patient’s own immune system to attack and kill cancer cells can lead to cancer cures and improved life spans for patients with many forms of cancer. However, there are still many patients whose tumors are resistant to immune therapy. We recently found that tumor associated macrophages, immune cells that are found in great numbers in tumors, cause resistance to immune therapy. We identified new drugs that break this resistance to immune therapy; these drugs led to cures in animals with cancer. We will test these drugs in patients with head and neck squamous cell carcinoma, monitoring for changes in biomarkers of immune suppression and tumor progression. We will also identify new immune therapy drug combinations that can improve cancer care. These studies will contribute to the development of novel, effective immune therapies for cancer patients.
Acute myeloid leukemia (AML) is a devastating cancer of the bone marrow resulting in progressive accumulation of leukemia cells and rapidly leads to bone marrow failure and death if not timely treated. In 2016, 20,000 new cases of AML and 10,000 disease-related deaths occurred in the United States alone. The median age at diagnosis is 67 years and the incidence of the disease increases with aging of the population. Estimated survival for AML patients diagnosed in the last 5 years in US is only 26.6%. Since 1969 only 5 drugs has been approved for treatment of AML. Therefore there is a clear unmet need for new and more active drugs. The current view is that AML treatment resistance or disease reoccurrence is due to the inability of current chemotherapy and/or molecular targeting drugs to eliminate the leukemia stem cells (LSC). These primitive malignant cells are capable of initiating and maintaining leukemia and are most resistant to current treatments. Here we propose to target and eliminate LSC by harnessing the immune system with newly synthesized bispecific antibodies and engineered T-cell cells aimed at IL1RAP, a protein that is preferentially expressed in LSC. Both these products are already in our hands and have a strong antileukemia activity and the ability to reduce LSC burden. Leveraging the infrastructure for drug development (including manufacturing facilities) already present at our Institution, we propose to complete preclinical, pharmacokinetic and pharmacodynamic studies and prepare for toxicology studies in order to move these products rapidly into the clinic.
Pancreatic cancer is highly lethal. Successful treatment may be possible if the cancer is identified early, but most pancreatic cancers are not caught until they have spread. Some pancreatic cancers start off as cysts, or fluid-filled sacs. Not all pancreatic cysts are cancerous though. It is easy to see pancreatic cysts using imaging tools like MRI, and to collect fluid from them using a biopsy procedure. However, we currently don’t have any good tests to determine which cysts are likely to become cancerous. We think the necessary information may lie in proteins contained in the pancreatic cyst fluid. Our project aims to create a test that will analyze the fluid to identify which cysts are cancerous and which are benign. By finding cancerous pancreatic cysts at an early stage, before they spread, we expect to be able to improve survival for patients. Our project will also help patients with benign cysts to avoid risky and expensive surgery. We also expect to learn more about the ways these special proteins play a role in the development of cancers in other bodily organs.
