The UCI Anti-Cancer Challenge is proud to announce the funding of a diverse range of innovative cancer research projects at the UCI Health Chao Family Comprehensive Cancer Center and its pediatric cancer affiliate, Children’s Hospital of Orange County (CHOC).
Through the unwavering support of dedicated participants, donors and supporters who collectively raised more than $1 million in 2022, the UCI Anti-Cancer Challenge has awarded grants to 28 pilot projects and early phase clinical trials, reaching a remarkable milestone of 100 funded projects since 2017. These projects are poised to revolutionize the future of cancer diagnosis, treatment and cures.
Click here to read the article on the 2022 UCI Anti-Cancer Challenge awardees announcement!
TRACK 1: PILOT PROJECTS
New Strategies to Overcome Therapeutic Resistance in Pancreatic Cancer
Aimee Edinger, PhD, VMD, Department of Developmental & Cell Biology, UCI School of Biological Sciences
Chris Halbrook, PhD (Co-Principal Investigator), Department of Molecular Biology and Biochemistry, UCI School of Biological Sciences
Pancreatic cancer is a dreaded diagnosis - most patients die within 5 years of learning they have the disease. Chemotherapy offers limited benefits, and new therapies that stimulate the body’s immune system to reject the tumor do not work well in pancreatic tumors. Our preliminary studies suggest that we have uncovered a new way that pancreatic cancers hide from the immune system. If we are correct, adding new drugs that have already been shown to be safe in humans to existing treatment regimens may help patients fight this terrible disease.
Optimizing the Impact of Social Media to Reduce Unmet Needs for Young Adult Cancer Survivors
Anamara Ritt-Olson, PhD, Department of Health, Society, and Behavior, UCI Program in Public Health
Joel Milam, PhD, (Co-Investigator), Department of Epidemiology and Biostatistics, UCI Program in Public Health
Candice Odgers, PhD, (Co-Investigator), Department of Psychological Science, UCI School of Social Ecology
Young adult survivors of cancer commonly experience unmet information needs concerning disease outcomes, ways to protect their mental and physical health, and ways to address daily struggles. There are locally available resources in Orange County that can help address many of these needs, but they remain underutilized. We will co-create with cancer community members a moderated Instagram site where survivors can share reviews about local resources with each other. We will test ways to increase motivation to review resources, ways to engage with the site, and will explore if reviews help survivors engage with local resources.
Using Single Cell Transcriptomics to Elucidate Fundamental Mechanisms of Cancer Surveillance
Arthur Lander, MD, PhD, Department of Developmental and Cell Biology, UCI School of Biological Sciences
Exciting breakthroughs in cancer treatment have recently come from stimulating the immune system, but treatments are successful only in some cases, and efforts to do better are hampered by a lack of understanding of how the immune system recognizes cancer cells and targets them for attack—a process called “immune surveillance”. Studies in animal models increasingly suggest that immune cells called macrophages scan the body specifically looking for patterns of growth that are not uniform, and selectively eliminating cells not growing like their neighbors. Using one of the simplest animal systems in which this process occurs—the fruit fly—we seek to identify the signals that recruit macrophages to such sites of “cell misbehavior”, so that we may translate a better understanding of immune surveillance into better cancer prevention and treatment.
Exploiting USP7 Inhibitors as a Therapeutic Approach In Osteosarcoma
Claudia Benavente, PhD, Department of Pharmaceutical Sciences, UCI School of Pharmacy and Pharmaceutical Sciences
Elyssa Rubin, MD, (Co-Principal Investigator), Bone and Soft Tissue Tumor Program, CHOC
Osteosarcoma is the most common primary bone cancer and occurs in adolescents and young adults. Metastasis remains the most important fatal complication in osteosarcoma. Thus, there is a pressing clinical need to develop new therapeutic strategies targeting the factors responsible for metastasis. We will establish the feasibility of exploiting novel developed compounds to prevent osteosarcoma metastasis. Further, we will work with Children’s Hospital of Orange County (CHOC) to develop a patient-derived xenograft tumor bank for OS which could be used to run future pre-clinical trials for novel compounds.
Connecting Mevalonate Pathway with Oncogene Transcriptional Networks in Leukemia
David Fruman, PhD, Department of Molecular Biology and Biochemistry, UCI School of Biological Sciences
Acute myeloid leukemia (AML) is a deadly blood cancer, and most patients respond poorly to current treatments. Our laboratory has discovered that widely used cardiovascular drugs called statins have potential to improve AML disease control by one of the current AML therapies. The goal of this project is to strengthen our understanding of how statins turn off survival signals in AML cells. Our ultimate goal is to translate this knowledge into new therapies that can improve the lives of AML patients.
Targeting Breast Cancer Metastasis with Natural Killer cells
Devon Lawson, PhD, Department of Physiology and Biophysics, UCI School of Medicine
Matthew Marsden, PhD (Co-Principal Investigator), Department of Microbiology and Molecular Genetics, UCI School of Medicine
The body’s immune system is a key player in cancer prevention. Previous work has shown that cancer cells can develop many different ways to evade the body’s immune system in order to grow and produce a tumor. One specific class of immune cells known as Natural Killer (NK) cells have an innate and potent ability to target and destroy cancer cells. In recent work, we found that cancer cells develop ways to inhibit this function of NK cells in order to metastasize and spread throughout the body. In this pilot project, we will use cutting-edge single cell genomics methods to determine the exact mechanism for how metastatic cells suppress NK cells. The goal of this project will be to use this knowledge to develop new ways to revive and boost NK cell function to target and destroy metastasizing cells.
Elucidating the Role of Gut Microbiome in Tamoxifen Pharmacokinetics
Elizabeth Bess, PhD, Department of Chemistry, UCI School of Physical Sciences
Cholsoon Jang, PhD (Co-Principal Investigator), Department of Biological Chemistry, UCI School of Medicine
Katrine Whiteson, PhD (Co-Investigator), Department of Molecular Biology and Biochemistry, UCI School of Biological Sciences
Although tamoxifen is used in nearly half a million people in the U.S. each year to prevent breast cancer recurrence, this drug is effective in only 50% of patients. Accurate prediction of which patients will receive the beneficial effects of tamoxifen is still lacking. Our initial studies show that a key to solving this mystery is likely in the human gut microbiome, which is markedly different between individuals and known to affect various drug effects. In this project, we will identify how gut bacteria control tamoxifen’s effectiveness, laying the foundation to predict a patient’s potential to benefit from tamoxifen therapy.
Interventions to Improve Lung Cancer Screening
Gelareh Sadigh, MD, Department of Radiological Sciences, UCI School of Medicine
Hari Keshava, MD, (Co-Investigator), Department of Surgery, UCI School of Medicine
Sunmin Lee, ScD, (Co-Investigator), Department of Medicine-Hematology/Oncology, UCI School of Medicine
Tan Nguyen, MD, (Co-Investigator), Department of Family Medicine, UCI School of Medicine
Michael Hoyt, PhD, (Co-Investigator), Department of Population Health and Disease Prevention, UCI Program in Public Health
Adherence to lung cancer screening remains low with multiple contributing patient- and provider-level barriers. Effective interventions to address such barriers among diverse populations and improve lung cancer screening adherence are lacking. Our study will assess perceptions and barriers towards lung cancer screening among a diverse racial/ethnic population-some of whom receiving care in community health centers- and their providers. We will test feasibility of a multilevel intervention addressing patient and providers’ barriers and use a mixed method approach to further refine our intervention for future larger effectiveness trials.
Quadruple Targeting Fabs (QT-Fab) for Pancreatic Cancer Treatment: Bispecific Fabs Conjugated to Two Anti-Cancer Therapeutics
Gregory Weiss, PhD, Department of Chemistry, UCI School of Physical Sciences
Despite many years of research, pancreatic cancer remains the third deadliest cancer. This proposal carefully considers what makes such cancers exceptionally resistant to conventional anti-cancer approaches and then uses new chemistry discovered in the PI’s lab to address prior limitations in pancreatic cancer treatment. Specifically, the proposal describes a new approach to the discovery of small antibodies requiring two halves to bind to tumor cells, insuring better specificity for only cancer cells, and then delivering two different cancer-specific drugs.
The Role of Vitamin D on Mast Cell Activation and Neuroinflammation in Paclitaxel-Induced Peripheral Neuropathy
Hyun Don Yun, MD, Department of Medicine-Hematology/Oncology, UCI School of Medicine/Long Beach VA
Breast cancer is the most common type of female cancer, but breast cancer treatment can cause severe nerve damages causing numbness, tingling and pain with a poor quality of life of the affected patients. The clinical strategies for the treatment or prevention of chemotherapy-related nerve damage are not well established. Often, the nerve damage related to chemotherapy is worsened by certain immune cells. Our research study will test the treatment effect of vitamin D in reducing the nerve damage caused by chemotherapy using human nerve and immune cells in laboratory.
Stress & Coping in Asian Americans with Advanced/Metastatic Cancer
Jacqueline Kim, PhD, Department of Medicine-Hematology/Oncology, UCI School of Medicine
Sunmin Lee, ScD (Co-Investigator), Department of Medicine-Hematology/Oncology, UCI School of Medicine
The social contexts and risk/resilience factors influencing the experiences of Asian Americans with advanced/metastatic cancer need to be better understood to improve quality of life. This pilot study will support larger funding allowing for deeper insights into how ethnoracial minority/immigrant experiences shape living with advanced/metastatic cancer. The long-term goal of this research is to suggest: 1) guidelines for screening of important social circumstances in cancer care, 2) next steps for psychosocial/behavioral interventions to buffer ethnoracial minority/immigrant-related stress, and 3) relevant biomarkers for improving patient-reported outcomes.
Evaluating BRCA-Mediated Ovarian Tumorigenesis and Metastasis Through Spatial Mapping and RNA-Sequencing at the Single-Cell Level
Kai Kessenbrock, PhD, Department of Biological Chemistry, UCI School of Medicine
Alyssa Bujnak, MD, (Co-Principal Investigator), Department of Obstetrics and Gynecology, UCI School of Medicine
Jill Tseng, MD, (Co-Principal Investigator), Department of Obstetrics and Gynecology, UCI School of Medicine
We seek to understand how ovarian tumors form and progress through studying the ovarian tissue and ovarian tumors of a group of patients with a mutation called BRCA, that are prone to developing ovarian cancer. We will use cutting edge technology allowing us to identify how individual cells in the ovary tissue and tumors are behaving and how they interact with neighbor cells. We theorize that certain types of cells in the ovaries of the patients with BRCA mutations are acting abnormally, causing other cells in the ovary to turn into cancer. This information may promote the development of methods to detect ovarian cancer earlier, and to create new treatments that will improve the lifespan of women with ovarian cancer.
"Image-guided Precision Radiotherapy" Team Science Seed Grant
Liangzhong Xiang, PhD, Department of Radiological Sciences, UCI School of Medicine
Charles Limoli, PhD, (Co-Principal Investigator), Department of Radiation Oncology, UCI School of Medicine
Zhongping Chen, PhD, (Co-Principal Investigator), Department of Biomedical Engineering, UCI School of Engineering
Thomas Milner, PhD, (Co-Principal Investigator), Department of Surgery, UCI School of Medicine
Vahid Yaghmai, MD, (Co-Principal Investigator), Department of Radiological Sciences, UCI School of Medicine
When treating cancer with radiation therapy, imaging is crucial to help plan and deliver the treatment effectively. However, with the emergence of a new type of radiation therapy called FLASH, which has potential benefits but also poses risks, new imaging techniques are needed to account for daily changes during treatment. Researchers are working on a new imaging modality called radiation-induced acoustic imaging, which will provide real-time 3D dose verification for FLASH therapy. This new technology will help ensure that the treatment is delivered precisely and accurately to the tumor and healthy tissues. This breakthrough can lead to a paradigm shift in using FLASH-RT for cancer treatment, which can benefit patients who may suffer from radiation-induced toxicities.
Multiomic Study of Merkel Cell Carcinoma Heterogeneity at the Single Cell Level
Ling Gao, MD, PhD, Department of Dermatology, UCI School of Medicine/Long Beach VA
MCC is far deadlier than melanoma, especially if not detected at early stage, with no effective targeted therapy and no definitive treatment for patients ineligible or resistant to immunotherapy. The increasing incidence of MCC is creating a growing impact on public health, particularly for Caucasian males between the ages of 60 and 85, who comprise nearly two-thirds of MCC patients and are well-represented within the Veteran population. Since the first FDA approval of immune checkpoint inhibitors, we still treat all MCC patients as one entity and more than half of metastatic MCC patients still succumb to their diseases, with median progression survival of only 2.7 months. This work will optimize the workflow in delineating MCC heterogeneity and fill in the clinical gaps.
Neuroblastoma with Resistance to Chemotherapy: A Therapeutic Strategy Based on Mitochondrial-Mediated Ferroptosis
M. Cristina Kenney, MD, PhD, Department of Ophthalmology, UCI School of Medicine
MYCN-amplified (MYCN-amp) neuroblastoma (NB) frequently spreads, is resistant to standard treatment and accounts for a significant portion of pediatric cancer fatalities. Ferroptosis is regulated cell death in which reactive oxygen species (ROS) are created through an iron-dependent process. We hypothesize that increasing levels of mitochondrial-mediated ferroptosis will inhibit the inflammation-related cGAS-STING pathway and cause the high-risk NB cells to lose their chemo-resistant property. We will investigate - (i) whether chemotherapy-resistant NB is sensitive to mitochondrial-dependent ferroptosis, and (ii) if ferroptosis plays a role in aggressive NB progression.
Impact of Personality on Adherence to Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Myeloid Leukemia
Mahtab Jafari, PharmD, Department of Pharmaceutical Sciences, UCI School of Pharmacy and Pharmaceutical Sciences
The personality and disposition of a patient may be a key factor that determines whether or not they follow the prescribed medication plan that has been laid out by their care provider. In turn, using treatment education strategies that are intentionally tailored to align with a patient’s personality may be a critical next step that healthcare providers can take to improve adherence. While some studies of other chronic diseases have found links between patients’ personalities and adherence, there is yet to be a study that specifically examines the personality of patients with chronic myeloid leukemia (CML) and how this might affect adherence to oral therapy with tyrosine kinase inhibitors such as imatinib. In this study, we will use a validated personality assessment and targeted interviews to gather data on 75 patients with CML in Orange County, which we will use to analyze the impact that patient personality might have on TKI adherence for those diagnosed with CML. Our findings will be useful in the design of future studies that utilize health coaches to improve the adherence of patients with CML to their therapy through an individualized program that takes personality into account.
Glucocorticoid Pre-Treatment of Mouse And Human Donor Grafts for Prevention of Graft-Versus-Host Disease While Maintaining Graft-Versus-Leukemia Response in Allogeneic Hematopoietic Cell Transplantation
Matthew Inlay, PhD, Department of Molecular Biology and Biochemistry, UCI School of Biological Sciences
Hematopoietic cell transplantation (HCT), also known as blood and marrow transplantation (BMT), is a potentially curative treatment for diseases of the blood, including blood cancers, where a patient’s diseased blood system can be completely replaced with that from a healthy donor. However, many risks remain, such as graft-versus-host disease (GvHD), caused when donor immune cells attack patient tissues, causing systemic inflammation, organ damage, and possibly death. The research in this proposal explores a potential treatment to prevent GvHD by manipulating the immune cells in the donor graft with glucocorticoids prior to transplantation. If successful, this research could improve the safety and efficacy of HCT and allow expansion of the pool of available donors for a patient to include haploidentical matches, which includes all parents and half of siblings.
Cell Therapy for Muscle Atrophy Following Irradiation in Rhabdomyosarcoma
Michael Hicks, PhD, Department of Physiology and Biophysics, UCI School of Medicine
Most cancer research focuses on new treatments and diagnostics such as through sequencing, yet few studies investigate how to improve quality of life for cancer survivors following current standards of care. Sarcomas are a group of deadly cancers that require aggressive radiotherapy to ablate the tumor; however, radiation often results in permanent dysfunction of nearby healthy tissues and long-term patient disability at the irradiation site. This research seeks to reconstruct new skeletal muscle following cancer radiotherapy using muscle stem cell therapy approaches.
Translating Goal-Focused Emotion Regulation Therapy to Young Adults Across Cancer Diagnoses
Michael Hoyt, PhD, Department of Population Health and Disease Prevention, UCI Program in Public Health
Jamie Frediani, MD, (Co-Principal Investigator), Adolescent and Young Adult Oncology Program, CHOC
Baolin Wu, PhD, (Co-Principal Investigator), Department of Epidemiology and Biostatistics, UCI Program in Public Health
Michelle Fortier, PhD, (Co-Principal Investigator), UCI Sue & Bill Gross School of Nursing
Establishing the ability to test the GET intervention in a broader population of young adult survivors expands the ability to meet the needs of a larger portion of our catchment area populations. The current study also increases the opportunities to partner with CHOC in the current project and the future clinical trial. This project will progress this work along the translational spectrum and is a necessary precursor to testing efficacy in a more representative population.
New Machine Learning Methods to Identify Metabolomic and Genomic Biomarkers for Colorectal Cancer
Min Zhang, MD, PhD, Department of Epidemiology and Biostatistics, UCI Program in Public Health
Mei Kong, PhD (Co-Principal Investigator), Department of Molecular Biology and Biochemistry, UCI School of Biological Sciences
The profiling of intermediary metabolites is emerging as an important platform for understanding the mechanisms underlying common chronic diseases, such as diabetes and cancer. Based on our successful identification of blood metabolomic biomarkers for colorectal polyps and the estimated genetic predisposition to colorectal cancer, we propose to identify metabolite and genomic biomarkers in animal models and human populations using our newly developed machine learning methods. The identified integrated metabolomic and genomic biomarkers will facilitate the early detection of colorectal cancer and improve disease risk prediction.
Quantifying Transarterial Embolization Outcome Using Optical Molecular Imaging
Nadine Abi-Jaoudeh, MD, Department of Radiological Sciences, UCI School of Medicine
Gultekin Gulsen, PhD, (Co-Investigator), Department of Radiological Sciences, UCI School of Medicine
Farouk Nouizi, PhD, (Co-Investigator), Department of Radiological Sciences, UCI School of Medicine
Assumptions that vessel occlusion of liver tumors will lead to ischemia have led to clinically mediocre patient outcomes. Understanding the consequences of transarterial embolization on tumor oxygenation is paramount. We propose to develop a dedicated CT-guided optical molecular imaging system to directly measure the changes in oxygenation levels and perfusion globally throughout the tumor before, during and after embolization in VX2 rabbit tumor model.
Flexible Fiber-Based Laser Micro-Biopsy Platform for Minimally-Invasive Tissue Collection and Processing During Cancer Surgery
Oliver Eng, MD, Department of Surgery, UCI School of Medicine
Thomas Milner, PhD (Co-Principal Investigator), Department of Surgery, UCI School of Medicine
Ryan O'Connell, MD (Co-Principal Investigator), Department of Pathology, UCI School of Medicine
Nitesh Katta, PhD (Co-Investigator), Beckman Laser Institute, University of California, Irvine
Colon cancer is one of the most common cancers worldwide and, in particular, accounts for a significant portion of patients who present to UCI for treatment. The management of colon cancer when it has spread or metastasized often requires biopsies to obtain tissue, which helps guide individualized treatment. Biopsy techniques and tissue processing have limitations and can be improved upon; therefore, we propose a novel platform which could potentially affect millions of patients annually.
Innate Immune Agonist Codrugs for Cancer Immunotherapy
Thomas Burke, PhD, Department of Microbiology and Molecular Genetics, UCI School of Medicine
Vy Maria Dong, PhD (Co-Principal Investigator), Department of Chemistry, UCI School of Physical Sciences
The innate immune system fights against infection by detecting pathogens and eliciting potent inflammatory responses. We propose to repurpose this signaling for cancer immunotherapy by synthesizing new small molecules that target multiple arms of the innate immunity to elicit synergistic inflammatory responses and to test these drugs in melanoma models in mice. These molecules could potentially be used to treat a variety of cancer indications and would work in combination with existing immunotherapies that activate adaptive immunity. These efforts will aid public health by advancing anti-cancer drugs towards the clinic and by establishing novel strategies for activating the immune system to fight cancer.
Is There a Link Between Prostate Cancer and HPV?
Wendy Cozen, DO, MPH, Department of Medicine-Hematology/Oncology, UCI School of Medicine
Arash Rezazadeh Kalebasty, MD (Co-Principal Investigator), Department of Medicine-Hematology/Oncology, UCI School of Medicine
Public health officials estimate 380 new cases of prostate cancer among Orange County men each year, with 22% of these diagnosed at late stage. Because of changes in screening, there has been an overall increase in late-stage prostate cancer. Unlike many cancers, there are no known behavior or other modifications shown to prevent prostate cancer (most of the known risk factors like, age, race/ethnicity and genetic factors, cannot be changed). There have been some reports that human papillomavirus (HPV) may be a risk factor for prostate cancer but there is no consensus. We are proposing a well-designed study of twins comparing a prostate cancer patient to their twin who never developed prostate cancer (the perfect control). We will measure previous exposure to HPV and two other infectious organisms by measuring antibodies which are unaffected by the cancer. If we can show a link between HPV and prostate cancer, it will provide a rationale to vaccinate boys with Gardasil, the HPV vaccine, for future prevention in Orange County, and to measure HPV antibodies in older men to justify continued screening with the prostate specific antigen test (PSA). Thus, the results would have a high impact on men in Orange County.
TRACK 2: EARLY PHASE CLINICAL TRIALS
A Phase II Study of Adding Pitavastatin to Venetoclax-Based Therapy in Acute Myeloid Leukemia (AML)
Elizabeth Brem, MD, Department of Medicine-Hematology/Oncology, UCI School of Medicine
David Fruman, PhD, (Co-Principal Investigator), Department of Molecular Biology and Biochemistry, UCI School of Biological Sciences
Some cancer cells take advantage of a protein called BCL2 to help them stay alive, and venetoclax (VEN) is an oral medicine that inhibits BCL2 to help kill cancer cells. Statins are medicines taken very commonly for the treatment of high cholesterol. Experiments done in the laboratory with cell lines and cells taken from people with leukemia suggest that statins may help VEN work better. In a phase 1 study, we have not seen any worse or different side effects when people took a statin called pitavastatin with VEN therapy for leukemia. Here, we propose a phase 2 study to help better understand if adding pitavastatin helps improve responses to VEN therapy for acute myeloid leukemia.
A Phase 1b Feasibility Trial of Response Adapted Neoadjuvant Therapy in Gastric Cancer (RANT-GC)
Farshid Dayyani, MD, PhD, Department of Medicine-Hematology/Oncology, UCI School of Medicine
Gastric cancer is the third leading cause of death from cancer globally, and despite the best current ‘one size fits all’ treatment of peri-operative chemotherapy and surgery, less than 50% of patients can be expected to be cured even in early-stage cancer. Importantly, only 50% of the patients can tolerate the required post-operative course of chemotherapy (e.g., due to slow recovery after surgery), which potentially contributes to worse outcomes. This proposal will use cutting edge molecular technology (i.e., tumor specific circulating tumor DNA in the plasma) to inform and personalize the pre-surgical treatment regimen used based on the individual tumor’s response, and hence maximize the upfront tumor shrinkage prior to curative intent surgery. Since all treatment is given before surgery, we also hypothesize that the patients will tolerate more of the expected chemotherapy those, further helping with eradicating the cancer completely.
A Pilot Study to Assess The Diversity Of Gut Microbiome in Metastatic Non-Small Cell Lung Cancer (NSCLC) in Correlation to Treatment Effects and Adverse Effects
Misako Nagasaka, MD, PhD, Department of Medicine-Hematology/Oncology, UCI School of Medicine
Approximately 40 trillion microbial cells are thought to live on and inside the human body and the largest number of microbial species reside in the gastrointestinal tract and are often referred to as “the gut microbiome.” In recent years, the imbalance of the gut microbiome, or dysbiosis, has been shown to be associated with different diseases including cancer. Constantly being exposed to numerous potential pathogens of the outer world, it is not surprising that the gut microbiome plays a critical role in the host immune response.
This pilot study aims to describe the effects of gut microbiome in lung cancer patients, particularly on how they may impact different treatment (immunotherapy, chemotherapy, and targeted therapy) by collecting and analyzing stool and saliva samples before treatment and at the time of their first imaging for treatment response. We expect high accrual of those considered to be of underrepresented minority (women, racial ethnic minorities) as targetable mutations have a higher prevalence in them. As such, this study is consistent with the CFCCC’s mission of inclusion.
Phase I Clinical Trial Using Donor-derived BK Virus-specific T-cells (BK-VSTs) for Patients Who Develop Hemorrhagic Cystitis after Allogeneic Stem Cell Transplantation (PIVOT)
Stefan Ciurea, MD, Department of Medicine-Hematology/Oncology, UCI School of Medicine
Catherine M. Bollard, MD (CNH), (Co-Principal Investigator), Center for Cancer and Immunology Research, Children’s National Hospital
Michael Daniel Keller, MD, (Co-Principal Investigator), Division of Allergy and Immunology Research, Children’s National Medical Center
Patrick J. Hanley, PhD, (Co-Principal Investigator), Cellular Therapy Program, Children’s National Medical Center
Piyanuch Kongtim, MD, (Co-Principal Investigator), Department of Medicine-Hematology/Oncology, UCI School of Medicine
Rishikesh Shahajirao Chavan, MD, (Co-Principal Investigator), Blood and Marrow Transplant Program, CHOC
Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative treatment option for patients with high-risk or advanced hematological malignancies. BK virus (BKV) infection after AHSCT has been associated with significant morbidity, prolonged hospitalization, and increased mortality in AHSCT recipients and can cause varying degrees of hemorrhagic cystitis (HC), obstruction of the urinary tract, kidney injury and nephritis. Treatment of HC is largely supportive with no effective drug therapy currently exists. Administration of third-party BK viral specific T cells (BK-VSTs) has been shown to effectively decrease BK uremia and improve symptoms of BK associated hemorrhagic cystitis (HC). However, the use of third-party BK-VSTs could increase the risk of graft versus host disease (GVHD) and decrease persistence of the T cells. In this study, we aim to determine the safety, feasibility as well as efficacy of donor-derived BK-VSTs for AHSCT recipients with BK viruria/viremia to prevent severe HC and decrease the risk of GVHD associated with third-party BK-VSTs.