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.
Black patients are more likely to die from breast, prostate, lung, and colorectal cancers than White patients. There are many reasons for these differences, including barriers to accessing treatment. In recent years, scientists have created new and better treatments that match a cancer’s unique biology, changing the way that we treat the disease. The first step to getting these therapies is genomic testing, which looks closely at the cancer to understand what might be causing it. Black patients are less likely to get genomic testing and these new therapies than White patients. If we don’t improve access to genomic testing, Black patients will continue to experience barriers to life-saving treatments, causing even bigger differences in survival between Black and White patients. In this study, we will look at the factors that cause differences in genomic testing between Black and White patients. We will also interview Black patients and cancer doctors about their experiences and preferences related to genomic testing. We will use our results to create strategies to improve access to genomic testing for Black patients. In the future, we hope to use our strategies at Duke Cancer Institute and in community hospitals in the Duke Cancer Network to reach cancer patients who are mostly Black, rural, and low-income, a group with large barriers to genomic testing.
Endometrial cancer (EC) is the most common cancer of the female reproductive tract inthe US. There has been an increase in the amount of this cancer and more women aredying of this than in the past. Black women are twice as likely to die from EC than whitewomen. There are many possible reasons for this, one of which might be that Blackwomen have different stressors than white women and this can change the way theimmune system works with chemotherapy to fight cancer. Our center is leading a one- of-a-kind research study dedicated to Black women with EC to better understand if anew immunotherapy treatment works as well in Black women as it does in whitewomen. We hope to look for markers that can help us predict if someone will respond tothe new treatment or not. These biomarkers can be used to help women decide if atreatment is right for them and are likely to be different between Black and whitewomen. We plan to look at three types of biomarkers: allostatic load (a measure of theimpact of stress on the body), microbiome (different bacteria make up in our bodies),and cytokines (markers of how our immune system is working). We hope to find out ifany of these biomarkers can help us predict which patients will respond to therapy andhelp improve outcomes for Black women.
Chimeric antigen receptor (CAR) T-cells are immune cells from patients that are engineered to target and kill cancers (not normal tissue). This is a new and exciting way to treat cancer. CARs have been wildly successful in treating children with leukemia that does not respond to any other therapy, saving many lives. I ran one of the first clinical trials to show this. Sadly, many patients experience severe or life-threatening side effects. The only drug that helps is currently on national shortage. This means some patients needing this lifesaving therapy may not get it. Even if that drug was available, CAR therapy still needs to be safer. We developed a chimeric inhibitory receptor (CIR) that we believe does just that. When it is combined with a CAR it dramatically decreases the production of the side effect causing proteins called cytokines. Importantly, it still kills tumors. Funding from this grant will allow us to make more versions of the CIR that can put the brakes on CARs in different ways. We will test the best ones in mice that have leukemia to confirm they still work. Results from these experiments will allow us to start a clinical trial of CIR-containing CAR T-cells for patients with leukemia or lymphoma here at the University of Virginia using our new CAR T-cell manufacturing facility. This unique approach to improving safety will have a dramatic impact on Virginians as well as all others with cancer who need life-saving CAR T-cell therapy.
