A5046273815- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- Lung Cancer Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Occupational and environmental lung diseases
- Immune Cell Function and Interaction
- Adenosine and Purinergic Signaling
- Tryptophan and brain disorders
- Virus-based gene therapy research
- Neuroendocrine Tumor Research Advances
- Immune cells in cancer
- Cancer therapeutics and mechanisms
- Histone Deacetylase Inhibitors Research
- Cancer Cells and Metastasis
- Cancer, Stress, Anesthesia, and Immune Response
- Monoclonal and Polyclonal Antibodies Research
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Hypoxia, and Metabolism
Duke University
2020-2025
Duke Cancer Institute
2019-2025
Duke Medical Center
2019-2025
Moffitt Cancer Center
2015-2024
LabCorp (United States)
2024
Duke Institute for Health Innovation
2023-2024
Piedmont International University
2021
Cancer Institute (WIA)
2020-2021
Aix-Marseille Université
2020
Inserm
2020
Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety BMS-936558, antibody that specifically blocks PD-1.
Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.
Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared docetaxel in this patient population.We randomly assigned 272 patients to receive at dose mg per kilogram body weight every 2...
Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy placebo in stage III NSCLC who did not after two or more cycles of platinum-based chemoradiotherapy.
An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for second primary end point of overall survival.We randomly assigned patients, a 2:1 ratio, to receive intravenously, at dose 10 mg per kilogram body weight, or matching placebo...
Abstract T cells infiltrating tumors have a decreased expression of signal transduction proteins, diminished ability to proliferate, and production cytokines. The mechanisms causing these changes remained unclear. We demonstrated recently that peritoneal macrophages stimulated with interleukin 4 + 13 produce arginase I, which decreases the T-cell receptor CD3ζ chain impairs responses. Using 3LL murine lung carcinoma model we tested whether I was produced in tumor microenvironment could...
Purpose Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated phase I trial expansion cohorts. We report overall survival (OS), response durability, long-term safety non–small-cell lung cancer (NSCLC) receiving nivolumab this trial. Patients Methods (N = 129) heavily pretreated NSCLC received 1, 3, or 10...
Antigen-presenting cells (APCs) can induce tolerance or immunity. We describe a subset of human APCs that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro. IDO-positive constituted discrete identified by coexpression the cell-surface markers CD123 CCR6. In dendritic (DC) lineage, IDO-mediated suppressor activity was present fully mature as well immature CD123+ DCs. IDO+ DCs could also be readily detected vivo, which suggests these may represent regulatory humans.
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing examine non-small-cell cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent PD-L1 expression the strongest feature associated efficacy multivariable analysis....
The phase III PACIFIC trial compared durvalumab with placebo in patients unresectable, stage non-small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation was associated significant improvements the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) progression-free (PFS [blinded independent central review; RECIST v1.1]; HR, 0.52; 0.42 0.65; < .0001), manageable safety. We report updated,...
One mechanism contributing to immunologic unresponsiveness toward tumors may be presentation of tumor antigens by tolerogenic host APCs. We show that mouse tumor-draining LNs (TDLNs) contained a subset plasmacytoid DCs (pDCs) constitutively expressed immunosuppressive levels the enzyme indoleamine 2,3-dioxygenase (IDO). Despite comprising only 0.5% LN cells, these pDCs in vitro potently suppressed T cell responses presented themselves and also, dominant fashion, third-party nonsuppressive...
Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies previously treated patients advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous 057; NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including pooled analysis of the studies. Methods Patients stage IIIB/IV (N = 272) 582) NSCLC and disease progression during after prior platinum-based...
Purpose In two phase III studies, nivolumab, a programmed death-1 (PD-1) inhibitor antibody, improved overall survival (OS) versus docetaxel in pretreated advanced non–small-cell lung cancer (NSCLC). We report 5-year follow-up results from an early I study of nivolumab this patient population and describe characteristics survivors. Patients Methods with pretreated, NSCLC received 1, 3, or 10 mg/kg every 2 weeks 8-week cycles for up to 96 weeks. OS the time first dose was estimated by...
Abstract Abnormal dendritic cell differentiation and accumulation of immature myeloid suppressor cells (ImC) is one the major mechanisms tumor escape. We tested possibility pharmacologic regulation using all-trans-retinoic acid (ATRA). Eighteen patients with metastatic renal carcinoma were treated ATRA followed by s.c. interleukin 2 (IL-2). Eight healthy individuals comprised a control group. As expected, cancer had substantially elevated levels ImC. observed that dramatically reduced number...
Checkpoint inhibitors targeting programmed cell death 1 or its ligand (PD-L1) as monotherapies in combination with anti-cytotoxic T-lymphocyte-associated antigen 4 have shown clinical activity patients metastatic non-small lung cancer.To compare durvalumab, without tremelimumab, chemotherapy a first-line treatment for cancer.This open-label, phase 3 randomized trial (MYSTIC) was conducted at 203 cancer centers 17 countries. Patients treatment-naive, who had no sensitizing EGFR ALK genetic...
Nivolumab, a monoclonal antibody that inhibits programmed cell death 1, is approved by the US Food and Drug Administration for treating advanced melanoma, renal carcinoma (RCC), non-small lung cancer (NSCLC), other malignancies. Data on long-term survival among patients receiving nivolumab are limited.To analyze overall (OS) identify clinical laboratory measures associated with tumor regression OS.This was secondary analysis of phase 1 CA209-003 trial (with expansion cohorts), which...
Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for NSCLC was evaluated the phase I, multicohort, Checkmate 012 trial.Fifty-two patients received 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment permitted per protocol. The primary objective to assess...