A5020001580- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Ovarian cancer diagnosis and treatment
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Cancer Research and Treatments
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Advanced Biosensing Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Occupational and environmental lung diseases
- Phagocytosis and Immune Regulation
- Galectins and Cancer Biology
- Microfluidic and Bio-sensing Technologies
- T-cell and B-cell Immunology
- Radiomics and Machine Learning in Medical Imaging
- Cell death mechanisms and regulation
- Intraperitoneal and Appendiceal Malignancies
- Cell Adhesion Molecules Research
- CRISPR and Genetic Engineering
- Genetic factors in colorectal cancer
- Reproductive System and Pregnancy
- Cancer, Lipids, and Metabolism
Gilead Sciences (United States)
2022-2024
University of Pennsylvania
2009-2023
Kite (United States)
2020
SRI International
2013-2019
Menlo School
2013-2018
Hospital of the University of Pennsylvania
2017
Cancer Research Center
1999-2016
Democritus University of Thrace
2013
Philadelphia University
2008-2012
Fred Hutch Cancer Center
1999-2011
Abstract Adoptive immunotherapies composed of T cells engineered to express a chimeric antigen receptor (CAR) offer an attractive strategy for treatment human cancer. However, CARs have fixed specificity such that only one tumor-associated (TAA) can be targeted, limiting the efficacy achieved because heterogeneous TAA expression. For this reason, more generalized and effective application CAR therapy would benefit from capability produce large panels against many known TAAs. In study, we...
Abstract Establishing a cancer screening biomarker's intended performance requires “phase III” specimens obtained in asymptomatic individuals before clinical diagnosis rather than II” from symptomatic at diagnosis. We used the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to evaluate ovarian biomarkers previously assessed phase II sets. Phase 180 cases 660 benign disease or general population controls were assembled four Early Detection Research Network Specialized...
Abstract T cell–based therapies have induced cancer remissions, though most tumors ultimately progress, reflecting inherent or acquired resistance including antigen escape. Better understanding of how cells eliminate will help decipher mechanisms. We used a CRISPR/Cas9 screen and identified necessary role for Fas–FasL in antigen-specific T-cell killing. also found that mediated off-target “bystander” killing antigen-negative tumor cells. This localized bystander cytotoxicity enhanced...
Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory large B lymphoma (LBCL) and has treatment with similar efficacy across conventional LBCL subtypes. Toward patient stratification, we assessed whether tumor immune contexture influenced clinical outcomes after axi-cel. We evaluated the microenvironment (TME) of 135 pre-treatment post-treatment biopsies taken from 51 patients in ZUMA-1 phase 2 trial. uncovered...
mAb OV569 was made by immunizing mice with ovarian carcinoma cells. It binds to cells from carcinomas and, a lesser extent, certain other whereas the binding normal tissues is low nondetectable. also soluble molecule(s) in culture supernatants antigen-positive carcinomas. recognizes protein(s) of 42–45 kDa same N-terminal amino acid sequence as membrane-bound portion mesothelin and megakaryocyte potentiating factor (MPF). Binding assays fusion proteins comprising either part mesothelin/MPF...
Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in identification protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models cancer been shown to faithfully recapitulate molecular, biological, clinical features disease. Here, we sought exploit merits a well-characterized GEM model pancreatic determine whether proteomics technologies allow development such are relevant cancer. Methods...
CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer biomarkers. Except for their behavior in the prediagnostic period has not evaluated.Immunoassays were used to determine concentrations of HE4, DcR3, proteins serum specimens (1-11 samples per participant) that contributed 0-18 years before diagnosis from 34 patients with (15 advanced-stage serous carcinoma) during a comparable time interval...
A quarter of a century since its discovery, circulating CA125 antigen is recommended for clinical use in the USA ovarian cancer screening high-risk women with ovaries, despite limited sensitivity and specificity. Recent findings suggest that might also serve as predictive marker pre-invasive carcinoma. Methods to quantify evolved toward sensitive reliable double-determinant ELISA assays. The gene, MUC16, was cloned 20 years after protein discovery revealed very complex unusual glycoprotein...
Abstract A panel of biomarkers may improve predictive performance over individual markers. Although many biomarker panels have been described for ovarian cancer, few studies used prediagnostic samples to assess the potential early detection. We conducted a multisite systematic evaluation using serum from Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial. Using nested case–control design, levels 28 were measured laboratory-blinded in 118 obtained before cancer diagnosis...
Cancer regression by gene-modified T cells bearing a chimeric antigen receptor (CAR) exodomain of mouse origin can be limited the induction transgene immunogenicity resulting in poor persistence and function vivo. The development functionally-active CAR human address this issue. Here, we constructed evaluated fully anti-mesothelin CARs comprised mesothelin-specific single-chain antibody variable fragment (P4 scFv) coupled to cell signaling domains. Primary expressing P4 specifically produced...
Abstract In melanoma, therapies with inhibitors to oncogenic BRAF V600E are highly effective but responses often short-lived due the emergence of drug-resistant tumor subpopulations. We describe here a mechanism acquired drug resistance through microenvironment, which is mediated by human tumor-associated B cells. Human melanoma cells constitutively produce growth factor FGF-2, activates tumor-infiltrating IGF-1. B-cell-derived IGF-1 critical for melanomas and MEK heterogeneous...
Complement activation plays a critical role in controlling inflammatory responses. To assess the of complement during ovarian cancer progression, we crossed two strains mice with genetic deficiencies transgenic that develop epithelial (TgMISIIR-TAg). TgMISIIR-TAg fully or partially deficient for factor 3 (C3) (Tg+C3KO and Tg+C3HET, respectively) C5a receptor (C5aR) (Tg+C5aRKO) either no tumors were small poorly vascularized compared to wild-type littermates (Tg+C3WT, Tg+C5aRWT). The...
B7-H4 (VTCN1, B7x, B7s) is a ligand for inhibitory coreceptors on T cells implicated in antigenic tolerization. expressed by tumor and tumor-associated macrophages (TAM), but its potential contributions to tumoral immune escape therapeutic targeting have been less studied. To interrogate expression cells, we analyzed fresh primary ovarian cancer collected from patient ascites solid tumors, established cell lines before after vivo passaging. was detected the surface of all human tumors...
Abstract Purpose: Efforts to validate ovarian cancer early detection biomarkers with immunoassays are challenged by the limited specimen volumes available. We sought develop a specimen-efficient assay measure CA125 in serum, assess its reproducibility, validity, and performance, test potential for multiplexing combining human epididymis protein 4 (HE4), promising novel marker. Experimental Design: Four pairs of commercially available anti-CA125 antibodies one pair anti-HE4 were evaluated...
Abstract Objective: To evaluate the effect of ovarian cancer risk on performance serum biomarkers mesothelin, human epididymis protein 4 (HE4), and CA125. Methods: We measured HE4, CA125 levels from women with invasive (n = 143), benign gynecologic conditions 124), controls 344). Demographic, epidemiologic, reproductive, medical, family history data were collected using a standardized questionnaire. Pedigree BRCA 1/2 test results used to stratify into average high-risk groups. The diagnostic...
Abstract We recently found that human CD83, a marker of mature dendritic cells, is an adhesion receptor binds to resting monocytes and subset activated CD8+ T cells. injected CD83-Ig into mice transplanted with the immunogenic P815 mastocytoma showed it significantly enhanced rate tumor growth inhibited development cytotoxic In contrast, immunized CD83-transfected K1735 poorly melanoma, could prevent outgrowth wild-type Studies performed in vitro PBL coimmobilized anti-CD3 cell proliferation...
Abstract To help determine CD83 function, a cDNA encoding soluble protein containing the extracellular domain was fused with mutated human IgG1 constant region (CD83Ig) and expressed by stable transfection of Chinese hamster ovary cells. Purified CD83Ig bound to peripheral blood monocytes subset activated CD3+CD8+ lymphocytes but did not bind FcR. Monocytes that had adhered plastic lost their ability after 90 min in vitro incubation. two five T cell lines tested, HPB-ALL Jurkat. The binding...
Abstract BACKGROUND. The current study sought to examine whether an index based on the specific pattern of symptoms commonly reported by women with ovarian cancer could be used in combination CA 125 improve sensitivity or specificity experimental methods screening for cancer. METHODS. A prospective case‐control design was used. Participants included 254 healthy at high risk disease because family history, and 75 Logistic regression analysis determine symptom predicted RESULTS. Symptom...
Epithelial ovarian cancer is a significant cause of mortality both in the United States and worldwide, due largely to high proportion cases that present at late stage, when survival extremely poor. Early detection epithelial cancer, serous subtype particular, promising strategy for saving lives. The low prevalence makes development an adequately sensitive specific test based on blood markers very challenging. We evaluated performance set candidate combinations these detecting cancer.We...
Abstract Objective: To evaluate if serum levels of candidate ovarian cancer biomarkers vary with individual characteristics healthy women who are likely candidates for an screening program. Methods: We analyzed CA125, mesothelin, and HE4 in a sample 155 postmenopausal at increased risk developing based on personal family history. Information reproductive, medical histories, lifestyle factors, anthropometry was collected by self-report. Twenty-two factors were examined using univariate...