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An NCI-designated Comprehensive Cancer Center, affiliated with the University of Pittsburgh School of Medicine
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Dr. Sabik is a health economist and health services researcher focused on investigating how state and federal policies affect healthcare access, utilization, and health outcomes among low-income and underserved populations, with a particular focus on cancer care. Recent and ongoing projects she leads examining the role of state health policy in access to cancer screening, timely diagnosis, and treatment for underserved groups have been funded by the National Cancer Institute, the Agency for Healthcare Research and Quality, and the American Cancer Society. She has also served as an investigator on a number of foundation-funded projects evaluating Medicaid policies and programs at the state and national levels and investigating issues related to the role of the healthcare safety net.
Dr. Saeed’s research efforts are focused on immune modulatory approaches in patients with gastric & esophageal cancer, colon cancer and hepatocellular carcinoma as well as chemoprevention/ immunoprevention in the high-risk GI population. She has published more than 150 peer reviewed papers, posters and book chapters, and have led more than 40 clinical trials, focused on various immune modulatory regimens including but not limited to immune checkpoint inhibitor combinations with chemotherapy, other checkpoint inhibitors, antibody drug conjugates, bi-specific T cell engagers (BiTE), angiogenesis inhibitors, as well as immunotherapy combinations with regional approaches like stereotactic radiosurgery and intensity-modulated radiation therapy. She currently lead several investigator-initiated trials focused on novel targeted immunotherapy combinations including the ongoing phase I/II CAMILLA multicohort study looking at Cabozantinib plus Durvalumab with or without Tremelimumab in GI malignancies. Results from phase I/II part of the CAMILLA led to the development of the currently ongoing global pivotal trial, STELLAR 303, in patients with previously treated microsatellite stable colorectal cancer. She is also the study chair for a soon to open SWOG/intergroup NCI national trial (S2303) testing a novel chemo-immunotherapy regimen in patients with advanced gastric & esophageal adenocarcinoma.
I am a clinical investigator who designs clinical trials in the space of colorectal cancer for drug development. My clinical research interests are targeted therapeutics and immunotherapy. I also collaborate with translational scientists to conduct correlative sciences. My translational research interests include understanding resistance mechanisms to immunotherapy, biomarkers analysis for immune response and investigating mechanisms of resistance to targeted therapy.
The Saloman lab focuses on how peripheral nerves shape the incipient tumor microenvironment. Current studies are designed to understand how sensory and sympathetic nerves regulate anti-tumor immunity and cancer pain. Several immune checkpoint proteins are expressed by the neurons that innervate the pancreas and ongoing experiments are investigating the role of these signaling molecules in regulation of the tumor microenvironment. Our overall goal is to understand the role of neural circuits to cancer biology and to harness this knowledge to improve early detection as well as identify targets for novel therapeutic approaches.
Dr. Sayette's research focuses on psychological theories of alcohol use and abuse, cigarette smoking, and drug craving, and on cognitive, affective, and social processes in addiction.
Head and neck squamous cell carcinoma (HNSCC) causes severe pain and stress, which exceeds the levels seen in other cancers. Beyond sensory/pain signaling, the peripheral nervous system has been identified as a component of the cancer microenvironment and may be involved in modulating tumor progression and tumor-associated immunity. The cancer microenvironment is comprised of stromal cells, glial cells, immune cells, neurons (e.g., motor, sensory, sympathetic) and proliferating tumor cells. The Scheff lab seeks to integrate the neurobiology, cancer biology, and immunology fields to fully appreciate neural-immune-cancer communication. The goal of our research is to understand plasticity in peripheral neurons associated with head and neck cancer and to investigate whether therapy targeted to neurons in the cancer microenvironment can alleviate pain and improve anti-tumor immunity. The lab executes translational research through collection of patient-reported outcomes and clinical specimens as well as implementation of molecular, electrophysiological and behavioral studies in preclinical mouse models.
My primary research interest is in the integration of palliative care services in oncology, with a particular focus on developing new models to improve provision of 'primary' palliative care within oncology practices. Secondary research interests include goals of care discussions, quality of life, healthcare policy in serious illness, surrogate decision making, informed consent, and the impact of language and cultural barriers on patient-clinician communication.
I am an exercise oncology researcher. My work focuses on large clinical trials related to physical activity and cancer, across the cancer control continuum, from primary prevention to addressing the needs of advanced cancer patients. The central mission of my work is to make exercise standard of care in oncology. Therefore, in addition to the efficacy trials my lab conducts, I am also actively involved in national and international efforts related to implementation of exercise for people living with and beyond cancer. UPMC Hillman Cancer Center is a vibrant community of science with an enormous network, which forms a tremendous platform from which to conduct both efficacy and implementation trials. The spirit of entrepreneurism at HCC allows innovation in keeping with my central mission. I currently lead 3 large NIH funded trials ranging from primary prevention to advanced cancer patients, all with an exercise oncology focus. In my role as leader of the exercise oncology initiative, my goal is to partner with the clinicians of HCC to discern the best ways to ensure that all cancer patients are informed about the benefits of exercise, supported to become active, and referred to appropriate resources (to include outpatient rehabilitation).
My work has appeared in JAMA, New England Journal of Medicine, JAMA Oncology, JNCI, and JCO, among other prestigious journals. I am the lead author on the first exercise guidelines for cancer patients and survivors from 2010, and senior author on the update from 2019. I have won numerous prestigious scientific awards, among them the Citation Award from the American College of Sports Medicine and the Distinguished Scientist Award from the Society of Behavioral Medicine.
My research interests center on applying a Quantitative Systems Pharmacology (QSP) approach that integrates experimental and computational analyses to understand disease and drug mechanisms, which will lead to developing more effective therapeutic strategies.
I am a PhD-prepared biostatistician and have collaborated with cancer researchers, primarily in the University of Pittsburgh School of Nursing, for more than 25 years in the area of behavioral and biomedical science, particularly symptom science and the possible toxic effects of cancer treatments and their impact on adherence to cancer treatments.
Dr. Shadel's research ranges from basic human laboratory work designed to understand the biopsychosocial mechanisms that contribute to smoking initiation and cessation, to the evaluation of cognitive-behavioral and pharmacological smoking cessation interventions in the clinic and public health settings. He has been continuously funded as a principal investigator by the National Cancer Institute and National Institute on Drug Abuse since 1999. Dr. Shadel's current grants examine how tobacco advertising contributes to adolescent smoking behavior, and the psychosocial mechanisms that underlie relapse in adult smokers.
The Shair Lab studies the human tumor virus “Epstein-Barr virus,” a ubiquitous herpesvirus with 90-95% seropositivity among adults worldwide. The resulting chronic infection can lead to EBV-associated cancer, which can occur in the immune-competent, and the immune-compromised such as post-transplant patients and HIV+ patients. A major focus is to translate these molecular studies to benefit cancer risk assessment and to elucidate EBV molecular pathogenesis in EBV-associated B-cell lymphomas and epithelial cell cancers. One EBV-associated cancer we study is nasopharyngeal carcinoma (NPC), a cancer with high prevalence in specific ethnic populations such as Alaskan Inuits and Southeast Asians. Our projects apply principles in molecular virology, epidemiology, and cell biology. One unique resource at our disposal is a biobank of primary nasopharyngeal cells that we built at the UPMC Hillman Cancer Center. These samples are used to address questions regarding the cellular response to EBV infection in the nasopharyngeal epithelium using techniques such as 3-D cell culture, single cell RNA-sequencing, and microscopy. Furthermore, by studying the molecular signature of the cellular humoral response to EBV antigens, we have profiled the antibody repertoire in persons known to be at risk of developing NPC. This information can be used to develop a risk assessment assay for NPC. We are a highly collaborative team of diverse scientists that tackle questions in molecular virology using interdisciplinary science.
The Sheikh lab is interested in understanding how various oncogenic drivers impact the response to DNA damage agents in pediatric CNS malignancies. Furthermore, we seek to determine how the alterations in the metabolome of pediatric CNS malignancies impact the response to DNA damage agents. Our ultimate goal is identify novel synergistic therapies that enhance the cell death response of pediatric brain tumors to DNA damage.
My primary research focus is on biobehavioral interactions in persons with cancer and neurologic conditions. I am particularly interested in the area of neuro-oncology, working with both patients and family caregivers to improve outcomes and health care delivery.
Dr. Shiffman's research focuses on tobacco use and nicotine dependence and their development, the nicotine withdrawal syndrome, smoking relapse, behavioral and pharmacological treatment for smoking, and tobacco control. Dr. Shiffman is currently conducting two trials, both focused on non-daily smokers, who are a substantial and growing fraction of adult smokers. The first study focuses on assessing the effects of switching to very low nicotine content cigarettes (VLNCCs) among intermittent smokers (ITS). This is a two-arm randomized study with an own-cigarette baseline control. After a 2-week baseline period smoking their own cigarettes, ITS will be randomized for 10 weeks to smoke experimental cigarettes, either (a) normal nicotine content cigarettes, or VLNCCs. Change in cigarette consumption is the primary end-point, and biomarkers of smoke exposure and measures of smoking intensity are also assessed. The second study focuses on the effect of as-needed oral Nicotine Replacement Therapy (NRT) for smoking cessation in ITS, and to study the process of relapse in ITS, using Ecological Momentary Assessment (EMA). Reviews of ITS have called for research on ITS' relapse process, and for evaluation of cessation methods, including medications, among ITS. This will be a double-blind, randomized, placebo-controlled trial of oral NRT for smoking cessation in ITS. EMA data collection includes two weeks of baseline data on ad lib smoking patterns and 6 weeks of post-quit data, using methods we successfully fielded in our previous research. This will capture data on craving, withdrawal, and relapse among ITS, and relate relapse contexts to baseline smoking patterns.
Studies on animal polyomaviruses have provided a wealth of information for cancer biology. Research on the simian and murine polyomaviruses (SV40 and PyV) led to the discovery of tumor suppressor proteins p53 and retinoblastoma (pRb) and unveiled the importance of tyrosine kinase activities in tumorigenic signaling. Our research exploits the human Merkel cell polyomavirus (MCV) that causes most Merkel cell carcinoma (MCC), a rare but deadly skin cancer that exhibits similarity to the tactile sensor “Merkel cells”. Despite the rarity of MCC, MCV infection is common, and nearly all healthy adults were asymptomatically infected and shed MCV from their skin. MCV is a small circular DNA virus that persists in currently unidentified dermal cells. There are two accidental events that are essential for MCV tumorigenesis and act as triggers that turn this common virus into a cancer-causing virus: insertion of linearized viral DNA into host cellular genome and introduction of a specific mutation that inactivates the viral replication enzyme.
By using molecular and cell biological approaches, our lab investigates: (1) MCV lifecycle processes, especially viral DNA replication, gene expression, and viral progeny production (2) MCV target cells wherein MCV persists or transforms into MCC, (3) biological triggers that disrupt the circular MCV DNA and facilitate insertion into host genome, and (4) critical cellular signaling activated by MCV proteins that promote MCC carcinogenesis. A full understanding of these events will help us prevent MCV-associated MCC, as well as identify therapeutic strategies for this deadly cancer.
Our research program focuses on the mechanisms of cellular and molecular interactions in the tumor microenvironment. The elements of the tumor microenvironment can collectively exert both stimulatory and inhibitory pressures on the proliferative, angiogenic, neurogenic and immunomodulating potential of cancerous cells, as well as their ability to spread and metastasize. Thus, insights into the mechanisms regulating host responses to growing tumors are essential for assessing relative risks and improving the therapeutic index for novel therapies associated with the modulation of the tumor microenvironment. Tumor-mediated immune suppression and tolerance remains a key obstacle to the safe and efficacious induction of antitumor immunity by immunotherapeutic modalities. Tumor innervation by afferent and efferent branches of the Peripheral Nervous System and intratumoral neuronal and neuroglial elements are responsible for attraction and activation of immune regulatory cells and for direct regulation of malignant cell proliferation, spreading and metastasis. Cytokines, chemokines, and regulatory RNAs derived from the neuroglial cells play the major role in this phenomenon. Our long-term goal is to develop a feasible and effective therapeutic approach based on a combination of pharmacological inhibition of specific MRC pathways and recovery/boosting of tumor specific immune responses.
My research has focused predominantly in the pathobiology of lung cancer and how the tumor microenvironment affects the natural biology and response to treatment. Working in collaboration with colleagues from the department of medical oncology we have discovered multiple possible biomarkers for disease management. In the future, I would like to integrate digital pathology analysis platforms into these studies. Specific topics of current investigation include: 1) Small cell lung carcinoma subtypes and genomics; 2) Morphologic features of lung cancer and its stroma, impact on natural biology; 3) Grading of Neuroendocrine Tumors; 4) Senescence in lung carcinoma immune response. In addition, in my role as the co-director of TARPS and as a member of TPIL, I hope to facilitate team based science, especially with regard to tissue based investigations.
My research focuses on the intersection of media and health, with a particular interest in investigating how we can use media and technology in ways that promote health. My work has examined the association between social media use and mental health outcomes, the spread of misinformation on social media, and online marketing of emerging tobacco products (e.g. hookah, e-cigarettes). Much of this work uses novel methodologies such as combining in-depth qualitative, quantitative, and social network data. I am currently conducting pilot trials in area high schools to test a media literacy-based tobacco prevention program as well as a large-scale study investigating nicotine and tobacco misinformation on youth-oriented social media platforms. As a part of my research, I utilize community-based participatory methods, especially when working with adolescents and emerging adults. I am also committed to developing the research, presentation, and publishing skills of undergraduate and graduate students by providing enriching mentoring opportunities.
Jonathan Silverstein, MD, MS, FACS, FACMI, serves as Chief Research Informatics Officer and Professor of Biomedical Informatics at University of Pittsburgh School of Medicine. He is internationally known for his expertise, and federally funded research, in the application of advanced computing architectures to biomedicine and on the design, implementation and evaluation of high-performance collaboration and visualization environments for anatomic education and surgery.
The primary research interests of the Singh laboratory include molecular characterization of novel cancer chemopreventive agents and rational design of mechanism-driven combination chemoprevention regimens. Cellular and transgenic animal models are used to screen potential cancer chemopreventive constituents from dietary and medicinal plants. Cutting edge cellular, molecular biological, omics (metabolomics and proteomics), structural biology, and imaging techniques (MRI and bioluminescence) are used to (a) determine the mechanism of action of promising cancer chemopreventive agents, (b) monitor effects on cancer progression, and (c) identify biomarkers predictive of tissue exposure and possibly response. Some of the agents under active investigation in the Singh laboratory include: cruciferous vegetable-derived isothiocyanates, garlic-derived organosulides, and medicinal plant constituent withaferin A. As an example, recent published work from the Singh laboratory indicates suppression of metabolism (glycolysis and fatty acid synthesis) in mammary cancer prevention by withaferin A in a rodent models. The Singh lab is also leading a clinical trial of broccoli sprout in prostate cancer patients.
Dr. Singhi's current research focus is primarily translational in the area of gastrointestinal, pancreatic, hepatobiliary and peritoneal pathology, and can be summarized in the following areas:
(1) Clinical diagnostic test development. In conjunction with other members of pathology, gastroenterology, surgical oncology and radiology, Dr. Singhi has been involved in the development of multiple clinical diagnostic tests for the evaluation of pancreatic cysts, biliary strictures, neuroendocrine tumors, and early detection of neoplasms involving the hepatopancreatobiliary tract. His research is supported by grants from the Pancreatic Cancer Action Network (PanCAN), National Pancreas Foundation (NPF), the University of Pittsburgh and the Institute for Precision Medicine (IPM) at the University of Pittsburgh. For more information regarding such tests as PancreaSeq (pancreatic cysts), BiliSeq (biliary strictures) and PanNeuroSeq (pancreatic neuroendocrine neoplasms), please refer to the Molecular & Genomic Pathology Laboratory website: http://mgp.upmc.com.
(2) Pathologic evaluation of non-neoplastic pancreatic pathology. In collaboration with several investigators, Dr. Singhi is involved in a multi-institutional effort to characterize various non-neoplastic pancreatic diseases, such as genetically and environmentally associated chronic pancreatitis.
(3) Co-director of the Biospecimen Repository and Processing Core (BRPC) of the Pittsburgh Liver Research Center (PLRC): http://livercenter.pitt.edu. Histopathologic and genetic characterization of peritoneal mesothelioma. In conjunction with members of the Division of Thoracic Pathology, Molecular & Genomic Pathology, and Surgical Oncology, Dr. Singhi's team has identified the genetic landscape of peritoneal mesothelioma with the goal of identifying biomarkers for prognostication and treatment stratification of patients.
(4) The epigenetic pathogenesis of pancreatic neuroendocrine tumors. In collaboration with investigators at the UPMC Division of Gastroenterology, Hepatology and Nutrition, and UPMC Hillman Cancer Center. This represents an international observational trial to evaluate prognostic biomarkers for pancreatic neuroendocrine tumors and determine the underlying epigenetic pathogenesis of these increasingly prevalent neoplasms.
Heath D. Skinner, MD, PhD, is a Professor in as well as the Chair of the Department of Radiation Oncology at the University of Pittsburgh and UPMC Hillman Cancer Center. In addition to his leadership and clinical duties, Dr. Skinner maintains an active, translational research laboratory focused upon identifying novel, clinically targetable biomarkers of resistance to radiation. His group utilizes "big data" approaches to clinical specimens as well as in vivo screening techniques to generate novel targets for study. These targets are then further investigated in vitro, to elicit insights regarding mechanisms of radioresistance. Dr. Skinner's research is designed to generate insights that led to the rational design of clinical trials using agents that are currently under investigation to minimize the time from bench to bedside. In addition to several current R01 grants, he is PI (along with Dr. Robert Ferris) of the UPMC Hillman Cancer Center Head and Neck SPORE.
In theory, inhibition of undesirable enzymatic activity responsible for disease can be accomplished either directly at the active site or indirectly at a distance (allostery). Important examples of selective enzyme inhibition come from the field of protein-tyrosine kinases, an emerging therapeutic target class for cancer and infectious diseases. Virtually all clinically useful kinase inhibitors to date compete for ATP binding at the kinase domain active site. However, the high degree of protein kinase sequence and structural homology limits the development of highly selective ATP-competitive kinase inhibitors. Alternative drug discovery avenues include allosteric inhibitors that target structural features outside of the kinase domain active site that are unique to individual kinase subfamilies. Allosteric inhibitor mechanisms are likely to exhibit greater specificity for their intended kinase targets, and may also stabilize kinase domain conformations that promote the action of existing inhibitors targeting the active site. Based on these principles, we are actively engaged in a drug discovery campaign to find small molecules that enhance the natural allosteric mechanisms associated with kinase domain regulation. We have developed high-throughput screening approaches based on this concept to identify selective inhibitors for protein-tyrosine kinases of the non-receptor class, including members of the Src, Fes/Fps and Abl kinase families. Selective inhibitors emerging from these screens have promise for future development in the treatment of several forms of leukemia, multiple myeloma, and HIV/AIDS.
The focus of the research in the laboratory is currently split into two major directions which are apparently distinct from each other with respect to the biological systems involved, their relation to the human disease, and experimental models used. However, the main idea underlying both directions is conceptually the same - to understand how endocytosis and post-endocytic trafficking regulates function(s) of the transmembrane proteins, such as receptors and transporters.
The first direction is the elucidation of the molecular mechanisms of endocytosis of growth factor receptors using a prototypic member of the family, epidermal growth factor (EGF) receptor, and analysis of the role of endocytosis in spatial and temporal regulation of signal transduction by the EGF receptor. The second direction is elucidating the role of trafficking processes in the regulation of dopaminergic neurotransmission by the plasma membrane dopamine transporter (DAT).
Dr. St. Croix is a tenured Professor of Cell Biology and an Associate Director of the CBI. She has been a PI or co-I on NIH-funded R01s, P01s and R21s, and has been continuously funded by the NIH since 2005. A major focus of the St. Croix laboratory is the use of advanced optical imaging technologies to dissect molecular signaling pathways controlling vascular function in rodent and zebrafish model systems of disease. Within the CBI, Dr. St Croix manages and directs the use and application of fluorescence-based optical microscopy with an emphasis on advanced tools multiparametric live cell microscopy, focused light intravital small animal imaging, super-resolution microscopy methods and complex image processing.
Dr. Stabile's laboratory is focused on the role of growth factors and hormones in the development of non-small cell lung cancer. Estrogen receptor signaling has been shown to be important in inducing proliferation in lung tumor preclinical models as well as promoting aggressive disease in lung cancer patients. We have demonstrated both genomic and non-genomic effects of estrogen in the lung and have elucidated cross-talk between the estrogen signaling pathway and multiple growth factor pathways including epidermal growth factor receptor, fibroblast growth factor receptor, hepatocyte growth factor and vascular endothelial growth factor. These preclinical studies have led to clinical trials examining the effectiveness of the anti-estrogen fulvestrant combined with targeted therapies for advanced stage lung cancer. Current interests include: 1) examining the mechanistic link between inflammation and estrogen signaling in lung carcinogenesis; 2) identification of dietary factors that modify lung cancer risk; and 3) development of novel therapeutic and prevention strategies involving hormonal manipulation and/or anti-inflammatory therapies in select high-risk populations.
Cell cycle dysregulation is a hallmark of every tumor. My lab uses quantitative single-cell microscopy and machine learning to study how the cell cycle changes during tumorigenesis, metastasis, and drug treatment, and the role of tumor microenvironment in regulating the proliferative state of a patient's tumor. Ultimately, our goal is to predict disease outcomes and therapeutic success by looking directly at the phenotype driving tumor growth — the cancer cell cycle.
My research interest including designing and testing novel psychosocial and behavioral interventions, including stepped collaborative care interventions, to improve quality of life in those with chronic medical conditions, psychoneuroimmunology, and caregiving.
Dr. Steinman has interrogated the function and regulation of cdk inhibitors during quiescence and differentiation. His recent research focuses on the contribution of platelets to tumorigenesis and on potential platelet-based urinary biomarkers of treatment efficacy. He also oversees three programs involving over 190 physician scientist trainees and conducts related educational research.
Dr. Donna Beer Stolz is the Associate Director of the Center for Biologic Imaging, University of Pittsburgh School of Medicine, and Professor in the Departments of Cell Biology and Pathology at the University of Pittsburgh. She has been the director of the Electron Microscopy arm if the CBI since 1997. Prior to arriving at the university, Dr. Stolz received her BS in Biochemistry in 1986 and a PhD in Molecular and Cellular Biology in 1991 from the University of Massachusetts, Amherst.
Dr. Stolz is the author/coauthor of over 370 publications from her work at the Center for Biologic Imaging as well as from her own research efforts. Her primary interests lie in coordinating imaging studies with investigators using transmission and scanning electron microscopy approaches and integrating a wide variety of optical and electron imaging technologies in cell biology. She is actively involved in medical and graduate student teaching.
Some of Dr. Stolz’s cancer-related outreach activities include:
My laboratory studies tumor immunobiology and designs immunotherapies for the treatment of cancer based on results from translational modeling. My near-term research goal remains the development of novel phase I/II clinical trials for the treatment of patients with cancer, with a focus on melanoma and renal cell carcinoma (RCC). Such treatment modalities include dendritic cell (DC)-based vaccines, cytokine gene-modified DC injected directly into tumor lesions and combination treatment approaches integrating agents that modulate tumor cell immune recognition and/or alter the balance or Type-1 versus regulatory immunity in the tumor microenvironment (TME). We discovered that immune targeting of the tumor-associated vasculature occurs naturally during effective immunotherapy, and that vaccines targeting tumor blood vessel antigens (TBVA) can promote tumor regression, even in cases where cancer cells themselves cannot be directly recognized by protective/therapeutic CD8+ T cells. Notably, even though these vaccines target normal non-mutated peptide sequences in TBVA proteins, no untoward (auto)immune-related pathology was observed in translational mouse modeling. We determined that treatment with anti-angiogenic agents leads to tumor vascular normalization and to the improved chemokine-dependent recruitment of therapeutic T cells into the TME, resulting in local formation of tertiary lymphoid structures (TLS) in association with slowed tumor growth and extended survival in animal models. We recently completed a pilot phase II clinical trial (UPCI 12-048/NCT01876212) evaluating combined treatment of HLA-A2+ patients with autologous aDC1/TBVA peptide vaccines + dasatinib (employed as an immune adjuvant). Vaccines were well tolerated by patients and we observed objective clinical responses in 46% of evaluable patients with advanced-stage cutaneous or uveal melanoma, including 57% of patients with prior demonstration of primary resistance to anti-PD1-based immunotherapy. Novel DC/TBVA peptide vaccines are currently being investigated in pilot phase II studies supported by NIH R01 (NCT05127824) and P01 (NCT04093323) in the setting of checkpoint-refractory advanced melanoma and early-stage renal cell carcinoma. We are also currently investigating the use of IRF3 agonists (including STING agonists) delivered directly into the TME as components of in situ vaccines in the advanced disease setting with the intent to promote formation of TLS in situ for improved local cross-priming of novel therapeutic anti-tumor B cell and T cell repertoires.
