A5060981161- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- Immune Cell Function and Interaction
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Immune cells in cancer
- Bacteriophages and microbial interactions
- Asthma and respiratory diseases
- T-cell and B-cell Immunology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Polyomavirus and related diseases
- Antenna Design and Analysis
- Peptidase Inhibition and Analysis
- Nanoplatforms for cancer theranostics
- Cancer, Hypoxia, and Metabolism
- Radiomics and Machine Learning in Medical Imaging
- Melanoma and MAPK Pathways
- Inhalation and Respiratory Drug Delivery
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Inflammation biomarkers and pathways
- Plant Virus Research Studies
- Lipid metabolism and biosynthesis
- Fibroblast Growth Factor Research
Yale University
2015-2024
University at Buffalo, State University of New York
1990
Human melanomas exhibit relatively high somatic mutation burden compared to other malignancies. These mutations may produce neoantigens that are recognized by the immune system, leading an antitumor response. By irradiating a parental mouse melanoma cell line carrying three driver with UVB and expanding single-cell clone, we generated mutagenized model exhibits burden. When inoculated at low numbers in immunocompetent C57BL/6J mice, YUMMER1.7 (Yale University Mouse Melanoma Exposed...
Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge cancer immunotherapy, and such patients, tumor-associated myeloid cells macrophages (TAMs) are promising therapeutic targets. We demonstrate an autochthonous, poorly immunogenic mouse model of melanoma that combination with agonistic anti-CD40 mAb CSF-1R potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single identified untreated...
Abstract Purpose: PD-1/PD-L1 inhibitors are approved for multiple tumor types. However, resistance poses substantial clinical challenges. Patients and Methods: We conducted a phase I trial of CD40 agonist APX005M (sotigalimab) CSF1R inhibitor cabiralizumab with or without nivolumab using 3+3 dose-escalation design (NCT03502330). were enrolled from June 2018 to April 2019. Eligibility included patients biopsy-proven advanced melanoma, non–small cell lung cancer (NSCLC), renal carcinoma (RCC)...
Abstract Recent advancements in single-cell technologies allow characterization of experimental perturbations at resolution. While methods have been developed to analyze such experiments, the application a strict causal framework has not yet explored for inference treatment effects level. Here we present causal-inference-based approach perturbation analysis, termed CINEMA-OT (causal independent effect module attribution + optimal transport). separates confounding sources variation from...
During the course of many chronic viral infections, antiviral T cell response becomes attenuated through a process that is regulated in part by host. While elevated expression immunosuppressive cytokine IL-10 involved suppression viral-specific responses, relevant cellular sources IL-10, as well pathways responsible for induction, remain unclear. In this study, we traced production over lymphocytic choriomeningitis virus (LCMV) infection an reporter mouse line. Using model, demonstrated...
<h3>Background</h3> PD-1 inhibitors are approved for multiple malignancies and function by stimulating T cells. However, the role of B cells in anti-tumor activity these drugs is unknown, as their patients who have received cell depleting or with immunoglobulin deficiencies. <h3>Methods</h3> We studied content 40 melanomas from treated pembrolizumab nivolumab assessed association response to therapy. Murine MC38 colon cancer YUMMER1.7 melanoma models were used determine whether concomitant...
Obesity is associated with colon cancer pathogenesis, but the underlying mechanism actively debated. Here, we confirm that diet-induced obesity promotes tumor growth in two murine models and show this effect reversed by an orally administered controlled-release mitochondrial protonophore (CRMP) acts as a liver-specific uncoupler of oxidative phosphorylation. This agent lowered circulating insulin, reduction was abrogated insulin infusion raising plasma to level high-fat-fed mice. We also...
Significance IL-7 and IL-15 have been shown to play crucial roles in maintaining the population of memory T cells, which are important fighting against secondary infections, but how effector cells receive these cytokines is incompletely understood. We investigated role C-C receptor 7 (CCR7) development using CCR7-deficient mice. showed an abnormal migratory pattern increased survival, especially lungs bone marrow, IL-15–dependent fashion compared with wild type cells. conclude that...
Memory T cells respond rapidly to repeated antigen exposure and can maintain their population for extended periods through self-renewal. These characteristics of memory have mainly been studied during viral infections, whereas existence functions in allergic diseases incompletely. Since patients suffer relapses caused by intermittent allergen exposure, we hypothesized that allergen- specific Th2 are present the factors necessary maintenance these provided lung airways. Using a murine model...
Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) like erlotinib are effective for treating patients with EGFR mutant lung cancer; however, drug resistance inevitably emerges. Approaches to combine immunotherapies and targeted therapies overcome or delay have been hindered by limited knowledge of the effect on tumor-infiltrating immune cells.Using mouse models, we studied immunological profile EGFR-driven tumors before after treatment.We found that triggered...
Metabolic homeostasis is one of the most exquisitely tuned systems in mammalian physiology. requires multiple redundant to cooperate maintain blood glucose concentrations a narrow range, despite multitude physiological and pathophysiological pressures. Cancer canonical settings which metabolism plays key role. In this study, we utilized REnal Gluconeogenesis Analytical Leads (REGAL), liquid chromatography-mass spectrometry/mass spectrometry-based stable isotope tracer method that developed...
Some patients have increased resistance in the nasal valve area that is static and does not collapse. Anterior rhinomanometry unable to document disorders these instances. A simple stent was devised open during anterior mask rhinomanometry. Three groups of subjects were studied with without stent. These 1) anatomic findings obstruction, 2) normal control subjects, 3) artificially created midseptal obstructions. At peak inspiration median decrease place when compared nonstented values 0.91...
<h3>Background</h3> Merkel Cell Carcinoma (MCC) is a rare cutaneous neoplasm of neuroendocrine origin associated with integration truncated form the Polyomavirus Large T Antigen (LTA) in ~80% U.S. cases.<sup>1</sup> LTA both antigenic and requisite for continued proliferation MCC, making it an attractive target therapeutic vaccine strategy.<sup>2</sup> <h3>Methods</h3> Expression was induced B16-F10 melanoma cell line to create <i>in vivo</i> murine MCC model. Modified mRNA coding produced...
Prospective and between trial comparisons indicate that first-line treatment with immune checkpoint inhibitors improves survival outcomes compared to therapy combined BRAF MEK in metastatic melanoma containing BRAFV600E/K mutations. Long-term for BRAF/MEK inhibition after progression on immunotherapy have not been reported. Moreover, clinical variables associated outcome from were previously identified the setting but investigated when targeted therapies are administered therapy. We...
2637 Background: Merkel Cell Carcinoma (MCC) is a neuroendocrine skin cancer associated with integration of truncated form Polyomavirus Large T Antigen (LTA) in most U.S. cases. LTA robust antigen and its expression required for proliferation MCC, rendering it an ideal target mRNA therapeutic vaccine approach. Methods: B16-F10 murine melanoma cells that express the oncoprotein were generated use as vivoMCC model. In vitro transcription was used to create optimized coding encapsulated lipid...
Abstract Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) like erlotinib are effective for treating patients with EGFR mutant lung cancer; however, drug resistance inevitably emerges. Approaches to combine immunotherapies and targeted therapies overcome or delay have been hindered by limited knowledge of the effect on tumor-infiltrating immune cells. Using mouse models, we studied immunological profile -driven tumors before after treatment. We found that triggered...
Abstract Fifteen percent of lung adenocarcinomas harbor mutations in the Epidermal Growth Factor Receptor (EGFR). Although EGFR mutant tumors show sensitivity to specific tyrosine kinase inhibitors (TKIs) like erlotinib, resistance develops after an average 12 months and there are currently no approved therapeutic strategies overcome resistance. Therefore, novel approaches delay improve patient survival crucial. Recent discoveries tumor immunology have revealed potential immune-based...
<p>Waterfall plots demonstrating the percent change in sum of RECIST v1.1 target lesions compared to baseline. Twenty-five out 26 patients were included; 1 patient withdrew consent and no follow-up imaging was available for review. The waterfall are color-coded by (A) best overall response (PR, SD, PD), (B) cohort (1-6), (C) tumor type (melanoma, RCC, NSCLC). majority who experienced disease progression on study had non-target lesions, as denoted asterisk (*), therefore from baseline...