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  • American Association for Cancer Research (AACR)  (3)
  • 2015-2019  (3)
  • Medicine  (3)
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  • American Association for Cancer Research (AACR)  (3)
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  • 2015-2019  (3)
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  • Medicine  (3)
RVK
  • 1
    Online Resource
    Online Resource
    First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors
    American Association for Cancer Research (AACR) ; 2019
    In:  Clinical Cancer Research Vol. 25, No. 1 ( 2019-01-01), p. 99-109
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 1 ( 2019-01-01), p. 99-109
    Abstract: The NHS-IL12 immunocytokine is composed of two IL12 heterodimers fused to the NHS76 antibody. Preclinical studies have shown that this antibody targets IL12 to regions of tumor necrosis by binding histones on free DNA fragments in these areas, resulting in enhanced antitumor activity. The objectives of this phase I study were to determine the maximum tolerated dose (MTD) and pharmacokinetics of NHS-IL12 in subjects with advanced solid tumors. Patients and Methods: Subjects (n = 59) were treated subcutaneously with NHS-IL12 in a single ascending-dose cohort followed by a multiple ascending-dose cohort (n = 37 with every 4-week dosing). Results: The most frequently observed treatment-related adverse events (TRAE) included decreased circulating lymphocytes, increased liver transaminases, and flu-like symptoms. Of the grade ≥3 TRAEs, all were transient and only one was symptomatic (hyperhidrosis). The MTD is 16.8 μg/kg. A time-dependent rise in IFNγ and an associated rise in IL10 were observed following NHS-IL12. Of peripheral immune cell subsets evaluated, most noticeable were increases in frequencies of activated and mature natural killer (NK) cells and NKT cells. Based on T-cell receptor sequencing analysis, increases in T-cell receptor diversity and tumor-infiltrating lymphocyte density were observed after treatment where both biopsies and peripheral blood mononuclear cells were available. Although no objective tumor responses were observed, 5 subjects had durable stable disease (range, 6–30+ months). Conclusions: NHS-IL12 was well tolerated up to a dose of 16.8 μg/kg, which is the recommended phase II dose. Early clinical immune-related activity warrants further studies, including combination with immune checkpoint inhibitors. See related commentary by Lyerly et al., p. 9
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-18-1512
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract 4595: Development and validation of a novel EGF receptor-neutralizing monoclonal antibody
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 4595-4595
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 4595-4595
    Abstract: The epidermal growth factor receptor (EGFR) is a cell-surface receptor for members of the epidermal growth factor family (EGF-family). EGFR dimerizes upon ligand binding, which leads to autophosphorylation, downstream signaling and ultimately internalization. In cancer, EGFR mutations and amplification have been linked to cell proliferation and survival. Two EGFR neutralizing monoclonal antibodies are currently FDA approved, which includes Cetuximab (Erbitux, BMS; mouse/human chimeric) and Panitumumab (ABX-EGF, Amgen; fully humanized). However, these antibodies are often unavailable to researchers studying this important pathway. Here we describe the development and validation of a new rabbit monoclonal EGFR neutralizing antibody (clone D1D4J). D1D4J was validated using cell-based models and immunofluorescence imaging. D1D4J binds EGFR and neutralizes EGF-induced activation and internalization. Compared to other Research Use Only (RUO) neutralizing antibodies on the market, D1D4J shows superior performance and is a useful research tool in the EGFR signaling space. Citation Format: Krystyna Zuberek Hincman, Christopher A. Manning, Michael R. Nelson, Michael Lewis, Roy Scialdone, Jaime Darce, Stephen R. Lutz, Evans Burford, Herbert Haack, Matthew R. Silver. Development and validation of a novel EGF receptor-neutralizing monoclonal antibody. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4595.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-4595
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Abstract 548: Exosome as biomarkers and diagnostics in bladder cancer
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 548-548
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 548-548
    Abstract: Esosomes are small membrane vesicles secreted by most cell types. They are first found in reticulocytes and play important roles in cell-to-cell communication. Recent studies suggest that exosomes secreted by tumor cells containing tumor specific proteins and miRNAs. Previous study shows that exosomes purified from high grade bladder cancer promote cancer progression. This study aims to characterize the genetic contents in bladder cancer exosomes through mass spectrometry and miRNA array. Exosomes were purified from bladder cancers, immortalized bladder cells, and urine of healthy volunteers and muscle invasive bladder cancer patients. Via proteomics analysis, we have identified several cancer associated exosomal proteins that were found only in bladder cancer, including EDIL-3, an anagiogenic protein in our previous report. Functional characterization of those proteins is currently undertaken with a focus on periostin an extracellulear matrix protein. In addition to protein, exosomes also contain miRNAs that regulate cellular behaviors. Thus, we performed miRNA expression profiling microarray on exosomes from high grade bladder cancer cells, and immortalized bladder cells (LC Sciences). The differences in miRNA expression were compared and differences were determined by a student T test (P & lt;0.05). Results showed significant difference miRNAs between cancer cells vs normal cells. Some of cancer-specific miRNAs which have shown to play critical roles in tumorigenesis and cancer progression will be study priority. Ultimately our work should contribute to the understanding of how exosomes contribute to bladder cancer biology and may elucidate novel urine exosomes markers for bladder cancer diagnosis. Note: This abstract was not presented at the meeting. Citation Format: Yu-Ru Liu, Christopher Silver, Yi-Fen Lee. Exosome as biomarkers and diagnostics in bladder cancer. [abstract] . In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 548. doi:10.1158/1538-7445.AM2015-548
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-548
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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