A5079791931- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Lung Cancer Research Studies
- Immune Cell Function and Interaction
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- HIV Research and Treatment
- Lung Cancer Diagnosis and Treatment
- Cancer Treatment and Pharmacology
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Systemic Lupus Erythematosus Research
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Growth Hormone and Insulin-like Growth Factors
- Neuroblastoma Research and Treatments
- Mesenchymal stem cell research
- Lymphoma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Sarcoma Diagnosis and Treatment
- Radiomics and Machine Learning in Medical Imaging
- HIV/AIDS drug development and treatment
Diamond Materials (United States)
2023-2024
City of Hope
2018
University of California, Irvine
2018
Cedars-Sinai Medical Center
2018
University of California, Los Angeles
2018
Clovis Oncology (United States)
2014-2017
Eli Lilly (United States)
2012-2016
SciClone Pharmaceuticals (United States)
2012
Rockefeller University
2003-2011
Memorial Sloan Kettering Cancer Center
2003-2011
During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage this process is that some the produced self-reactive. We determined prevalence self-reactive antibody formation and its regulation in human cells. majority (55 75%) all expressed early immature cells displayed self-reactivity, including polyreactive anti-nuclear Most these autoantibodies were removed from population at two discrete...
A cardinal feature of systemic lupus erythematosus (SLE) is the development autoantibodies. The first autoantibodies described in patients with SLE were those specific for nuclei and DNA, but subsequent work has shown that individuals this disease produce a panoply different Thus, one constant features profound breakdown tolerance antibody system. appearance self-reactive antibodies precedes clinical disease, where B cell pathway broken not been defined. In healthy humans, are removed from...
Autoantibodies are removed from the repertoire at two checkpoints during B cell development in bone marrow and periphery. Despite these checkpoints, up to 20% of antibodies expressed by mature naive cells healthy humans show low levels self-reactivity. To determine whether self-reactive also part antigen-experienced memory compartment, we analyzed recombinant cloned single circulating human IgM+ cells. Cells expressing specific for individual bacterial polysaccharides were expanded...
A majority of the antibodies expressed by nascent B cells in healthy humans are self-reactive, but most these removed from repertoire during cell development. In contrast, untreated systemic lupus erythematosus (SLE) patients fail to remove many self-reactive and polyreactive naive repertoire. Here, we report that SLE clinical remission continue produce elevated numbers mature compartment, number expressing is lower than with active disease. Our finding abnormal levels persist suggests early...
HIV entry into human cells is mediated by CD4 acting in concert with one of several members the chemokine receptor superfamily. The resistance to infection observed individuals defective CCR5 alleles indicated that this particular plays a crucial role initiation vivo infection. Expression transgene does not render mice susceptible because structural differences between and mouse CCR5. To ascertain whether expression sufficient make murine T lymphocytes infection, lck promoter was used direct...
Long-term humoral immunity is maintained by the formation of high-affinity class-switched memory B cells and long-lived antibody-secreting plasma cells. In healthy humans, a substantial fraction IgG-positive express self-reactive polyreactive IgG antibodies that frequently develop somatic mutations. Whether self- IgG-secreting are also tolerated in cell pool not known. To address this question, we cloned expressed Ig genes from 177 IgG-producing bone marrow four donors. All were highly...
BACKGROUND Vascular endothelial growth factor (VEGF)–mediated angiogenesis plays an important role in non–small cell lung cancer (NSCLC). Ramucirumab is a human immunoglobulin G1 monoclonal antibody that inhibits VEGF receptor 2. This phase 2 study investigated ramucirumab combination with first‐line pemetrexed and platinum chemotherapy advanced/metastatic NSCLC. METHODS Eligible stage IV nonsquamous NSCLC patients no prior for metastatic disease were randomized 1:1 to carboplatin (or...
8001 Background: Rociletinib is an oral inhibitor of mutant EGFR, including the T790M resistance mutation. We reported robust activity in positive pts identified by tumor genotyping treated at 500mg-1000mg BID (active doses) [NCT01526928]. now present data from pt subset with detected plasma genotyping. Methods: For overall phase 1/2 study, had EGFR-mutant NSCLC and treatment ≥ 1 EGFR inhibitor, ECOG PS 0-1. Brain metastases were allowed. In 2, pos central was required. Plasma status...
The objective of this study was to determine whether the addition ramucirumab first-line paclitaxel-carboplatin chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) resulted a 6-month progression-free survival (PFS) rate that compares favorably historic for bevacizumab combined patient population.In phase II, single-arm, open-label, multicenter study, 40 NSCLC received (10 mg/kg intravenous [IV]) followed by paclitaxel (200 mg/m IV) and carboplatin area under curve = 6...
This pediatric phase I study was designed to identify the doses of RG1507, a monoclonal antibody against Type 1 Insulin-like Growth Factor Receptor (IGF1R), that achieves exposures equivalent those achieved in adults at recommended doses.Children with relapsed or refractory solid tumors were treated using same and administration schedules RG1507 (3 9 mg/kg/wk, 16 mg/kg every 3 weeks [q3W]) as studied adults. Detailed pharmacokinetic (PK) sampling performed after first dose; selected peak...
9001 Background: Rociletinib is an oral inhibitor of mutant EGFR, including T790M. We compared EGFR mutation detection in circulating tumor DNA from blood and urine to that matched tissue TIGER-X (NCT01526928), a phase 1/2 study rociletinib pts with EGFRpositive advanced NSCLC. Methods: status was assessed by the therascreen test (Qiagen) tissue, BEAMing (Sysmex) plasma, quantitative short footprint assay method uses next-generation sequencing (Trovagene) urine. Results: Of 417 500 625 mg...
CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with potent TLR-4 agonist. This open-label randomized phase II trial was designed investigate efficacy safety of adding atezolizumab (anti-programmed death ligand-1 therapy) in comparison alone patients synovial sarcoma or myxoid liposarcoma.Patients locally advanced, relapsed, metastatic liposarcoma (any grade) were randomly assigned...
Abstract Background Outcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series post hoc analyses clinical trials. Methods In this multi‐center study, were abstracted from the medical records 350 patients nine centers throughout United States combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) MRCL 101) who received first‐line systemic anticancer therapy had...
TPS9156 Background: The epidermal growth factor receptor (EGFR) is a potent oncogene commonly altered in many cancers, including glioblastoma (GBM) and non-small cell lung cancer (NSCLC). EGFR tyrosine kinase activity driven by common mutations can be inhibited small molecules, however, resistance to available agents may the active site or other regions. BDTX-1535 an orally available, highly potent, selective, irreversible inhibitor of mutations, extracellular variants amplifications...
Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, preliminary efficacy intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study comprised dose escalation (5 or 10 µg/dose, 20 µg/dose for large tumors); randomized...
LBA8006^ Background: RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The REVEL study evaluated efficacy and safety RAM+DOC vs. PL+DOC (DOC) in patients (pts) with stage IV nonsquamous (NSQ) squamous (SQ) NSCLC after platinum-based therapy. Methods: Pts NSQ SQ were randomized 1:1 (stratified by sex, region, ECOG PS, prior maintenance therapy) to receive DOC 75 mg/m 2 combination either 10 mg/kg or PL on day 1 21-day cycle until disease progression,...