A5086165685- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- Virus-based gene therapy research
- Cancer Research and Treatments
- Metabolism, Diabetes, and Cancer
- Melanoma and MAPK Pathways
- Monoclonal and Polyclonal Antibodies Research
- Cutaneous Melanoma Detection and Management
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Macrophage Migration Inhibitory Factor
- Microtubule and mitosis dynamics
- Viral Infectious Diseases and Gene Expression in Insects
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Head and Neck Cancer Studies
- Protein Kinase Regulation and GTPase Signaling
University of Louisville
2016-2025
James Graham Brown Foundation
2014-2025
GTx (United States)
2007-2018
University of Iowa Hospitals and Clinics
2017
University of North Carolina at Chapel Hill
2017
Roswell Park Comprehensive Cancer Center
2017
Dana-Farber Cancer Institute
2017
Deaconess Hospital
2017
Memorial Sloan Kettering Cancer Center
2017
Cornell University
1905-2017
In a phase 1 dose-escalation study, combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with high rate objective response, including complete responses, among patients advanced melanoma.
Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients unresected stage IIIB IV melanoma randomized open-label phase III trial.Patients injectable that not surgically resectable were randomly assigned at two-to-one ratio intralesional or...
The protein known as macrophage migration inhibitory factor (MIF) was one of the first cytokines to be discovered and described 30 years ago a T-cell-derived that inhibited random macrophages in vitro. A much broader role for MIF has emerged recently result studies have demonstrated it released from anterior pituitary gland vivo. also is been identified secreted monocytes/macrophages upon glucocorticoid stimulation. Once released, acts "override" or counter-regulate suppressive effects...
The importance of the macrophage in innate immunity is underscored by its secretion an array powerful immunoregulatory and effector molecules. We report herein that migration inhibitory factor (MIF), a product activated macrophages, sustains survival function suppressing activation-induced, p53-dependent apoptosis. Endotoxin administration to MIF −/− mice results decreased viability, proinflammatory function, increased apoptosis when compared with wild-type controls. Moreover, inhibition p53...
Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus alone in patients with advanced melanoma a phase II study. To our knowledge, this was first randomized trial to evaluate addition an oncolytic virus checkpoint inhibitor. Methods Patients unresectable stages IIIB IV melanoma, no more than one prior therapy if BRAF wild-type, two therapies mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant...
CheckMate 568 is an open-label phase II trial that evaluated the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line treatment advanced/metastatic non-small-cell lung cancer (NSCLC). We assessed association with programmed death ligand 1 (PD-L1) expression tumor mutational burden (TMB).Two hundred eighty-eight patients previously untreated, recurrent stage IIIB/IV NSCLC received 3 mg/kg every 2 weeks 6 weeks. The primary end point was objective response rate (ORR) in 1%...
Loss of membrane MHC class I protein expression in most tumor cells advanced melanomas predicts primary resistance to anti–CTLA-4, but not anti-PD1, treatment.
Abstract 6-Phosphofructo-1-kinase, a rate-limiting enzyme of glycolysis, is activated in neoplastic cells by fructose-2,6-bisphosphate (Fru-2,6-BP), product four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isozymes (PFKFB1-4). The inducible PFKFB3 isozyme constitutively expressed and required for the high glycolytic rate anchorage-independent growth ras-transformed cells. We report herein computational identification small-molecule inhibitor PFKFB3,...
Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined ipilimumab in clinical trials discontinued treatment because adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety plus AEs. Methods Data were pooled from phase II III 1 mg/kg 3 mg/kg, every weeks for four doses, followed by monotherapy 2 (N = 409). Efficacy was assessed all randomly assigned AEs during induction (n 96) those did not discontinue 233). Safety...
Abstract Introduction Glycolysis is increased in breast adenocarcinoma cells relative to adjacent normal order produce the ATP and anabolic precursors required for survival, growth invasion. also serves as a key source of reduced form cytoplasmic nicotinamide adenine dinucleotide (NADH) necessary shuttling electrons into mitochondria electron transport. Lactate dehydrogenase (LDH) regulates glycolytic flux by converting pyruvate lactate has been found be highly expressed tumours. Aspartate...
Effective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in melanoma. Lifileucel is an autologous, centrally manufactured lymphocyte product.We conducted a phase II open-label, single-arm, multicenter study had been previously treated inhibitor(s) BRAF ± MEK agents. was produced from...
In human cancers, loss of PTEN, stabilization hypoxia inducible factor-1α, and activation Ras AKT converge to increase the activity a key regulator glycolysis, 6-phosphofructo-2-kinase (PFKFB3). This enzyme synthesizes fructose 2,6-bisphosphate (F26BP), which is an activator 6-phosphofructo-1-kinase, step glycolysis. Previously, weak competitive inhibitor PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), was found reduce glucose metabolism proliferation cancer cells. We have...
Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes 153 treated lifileucel large multicenter Phase 2 therapy trial melanoma.Eligible had that...
The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile encouraging complete response rate (CRR) in patients with advanced melanoma a phase Ib study. We report the efficacy from III, randomized, double-blind, multicenter, international study T-VEC plus (T-VEC-pembrolizumab) versus placebo (placebo-pembrolizumab) melanoma.Patients stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were...
Talimogene laherparepvec (T-VEC) plus ipilimumab has demonstrated greater antitumor activity versus alone, without additional toxicity, in patients with advanced melanoma. Here, we report the 5-year outcomes from a randomized phase II study. These data provide longest efficacy and safety follow-up for melanoma treated combination of an oncolytic virus checkpoint inhibitor.Eligible unresectable stage IIIB‒IV were 1:1 to receive T-VEC or alone. was administered intralesionally at 106...
We recently described a novel population of blood-borne cells, termed fibrocytes, that display distinct cell surface phenotype (collagen+/CD13+/CD34+/CD45+), rapidly enter sites tissue injury, and contribute to scar formation. To further characterize the role these cells in vivo, we examined expression type I collagen cytokine mRNAs by isolated from wound chambers implanted into mice. Five days after chamber implantation, CD34+ fibrocytes but not CD14+ monocytes or CD90+ T expressed mRNA for...
Recent studies have identified a novel population of blood-borne cells, termed fibrocytes, that distinct cell surface phenotype (collagen + /CD13 /CD34 /CD45 ), rapidly enter sites tissue injury, and synthesize connective matrix molecules. We found by flow cytometry purified human fibrocytes express each the known components are required for antigen presentation, including class II major histocompatability complex molecules (HLA-DP, -DQ, -DR), costimulatory CD80 CD86, adhesion CD11a, CD54,...