15 research outputs found
Auchenorrhyncha and Psylloidea collected during the 25th Central European Auchenorrhyncha meeting, Arnhem, The Netherlands (Hemiptera: Auchenorrhyncha and Psylloidea)
Die 25. MitteleuropĂ€ische Zikadentagung fand vom 14.-17. September 2018 in Arnheim in den Niederlanden statt. Da es die erste Tagung in den Niederlanden war, wurden Sammelexkursionen in fĂŒnf typische niederlĂ€ndische Landschaften unternommen. Drei der Exkursionsziele befanden sich in neu geschaffenen Schutzgebieten, die sich auf ehemals landwirtschaftlich genutzten FlĂ€chen befinden. Die beiden weiteren Exkursionsziele waren alte, geschĂŒtzte HeideflĂ€chen. Insgesamt konnten 117 Zikadenarten und 6 Psylloidea-Arten nachgewiesen werden. Drei Arten waren neu fĂŒr die Niederlande: Macrosteles spinosus (in dieser Publikation vorgestellt), Kybos abstrusus (monophag an Populus nigra) und Macrosteles sardus (an Epilobium hirsutum). FĂŒr einige seltene Arten konnten neue Fundpunkte ermittelt werden: Kelisia monoceros, Aphrophora major, Stroggylocephalus agrestis, Edwardsiana diversa, E. tersa, Fruticidia bisignata, Ophiola russeola und Psammotettix pallidinervis. Durch die drei Neufunde erhöht sich die Anzahl der bislang in den Niederlanden nachgewiesenen Zikadenarten auf 421. Diese Arbeit zeigt zudem, dass selbst in erst seit kurzem bestehenden Schutzgebieten seltene und interessante Arten nachgewiesen werden können. The 25th Central European Auchenorrhyncha meeting took place in Arnhem, The Netherlands on 14-17 September 2018. It was the first time the meeting was held in The Netherlands, and for this reason, excursions were undertaken to five typical Dutch landscapes. Three of the excursions involved newly created nature reserves, located on former agricultural land. The other two were old, protected heathlands. In total, 115 Auchenorrhyncha species, and 6 Psylloidea species were collected. Three species were new for the Netherlands: Macrosteles spinosus (presented in this paper), Kybos abstrusus (monophagous on Populus nigra) and Macrosteles sardus (Epilobium hirsutum). For a number of rare species new occurrences were reported: Kelisia monoceros, Aphrophora major, Stroggylocephalus agrestis, Edwardsiana diversa, E. tersa, Fruticidia bisignata, Ophiola russeola and Psammotettix pallidinervis. Our results show that also in young, newly created nature reserves interesting species can be found. 
When Simpler Is Better. Unicellular Green Algae for Discovering New Genes and Functions in Carbohydrate Metabolism
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Characterization of neoepitope (neoE)-specific T cells from peripheral blood for adoptive neoTCR-T cell therapy for patients with breast cancer (bc) or ovarian cancer (oc).
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Abstract 331: Characterization of neoepitope (neoE)-specific T cells from peripheral blood for adoptive neoTCR-T cell therapy for patients with breast cancer (bc) or ovarian cancer (oc)
Abstract
Introduction: Broad application of neoTCR-T cell therapy involves isolation of mutation-targeted CD8 T cells from the blood of patients with different tumor types. An ultra-sensitive process streamlined for high-throughput capture of neoE-specific T cells from blood is leveraged for producing a fully personalized adoptive T cell therapy for trial participants with BC or OC (NCT03970382).
Methods: Expressed mutations were identified by comparative sequencing of blood cells and tumor tissue. HLA typing was performed with OpiType. Proprietary algorithms were used to predict and prioritize tumor-exclusive neoE-HLA candidates. A library of barcoded HLA-mutational neoantigen complexes was used to interrogate PBMCs from each patient using imPACT Isolation TechnologyÂź (Dalmas et al., 2020). NeoTCRs cloned from captured antigen-experienced CD8 T cells were precision genome engineered into healthy donor T cells for functional characterization, including secretion of cytokines and effector molecules (Jacoby et al., 2019; Sennino et al., 2019). Based on pre-specified prioritization criteria, up to 3 actionable neoTCRs were selected for manufacturing the products for each individual.
Results: Six patients (2 BC/4 OC) successfully underwent neoTCR product selection. The median age was 59.5 years (range 38-69). Patients received a median of 5.5 prior regimens for metastatic disease (range 4-9). Median tumor mutational burden (TMB) was 2.7 (range 0.9-13.4). HLA-neoantigen libraries contained a median of 91 snares (range 29-262) and represented 6/6 HLA alleles in 4 patients and 5/6 in the remaining 2. A median of 8.5 distinct neoE-specific T cells (range 5-15) were isolated per patient. Following functional characterization 13 neoTCRs met selection criteria: three patients with 3 TCRs, one with 2 TCRs, and two had a single TCR. The median predicted neoE:HLA affinity of the selected TCRs was 77 nM (range 6.3 - 5866) and the median IFN-g EC50 was 4 ng/mL (range 1-431).
Conclusion: Relevant antigen-experienced, tumor mutation-targeted CD8 T cells were isolated from the blood of heavily pre-treated BC and OC patients with low TMB (<10 mutations/Mb). Correlations between TCR characteristics and clinical and biomarker data are planned. This approach holds potential for broad use in women with BC or OC.
Citation Format: Mihaela Cristea, Bartosz Chmielowski, David Y. Oh, Roel P. Funke, Daniela A. Bota, Mehrdad Abedi. Characterization of neoepitope (neoE)-specific T cells from peripheral blood for adoptive neoTCR-T cell therapy for patients with breast cancer (bc) or ovarian cancer (oc) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 331
Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC).
Safety and efficacy of MPDL3280A (anti-PDL1) in combination with platinum-based doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).
Clinical activity and safety from a phase II study (FIR) of MPDL3280A (anti-PDL1) in PD-L1âselected patients with non-small cell lung cancer (NSCLC).
Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy
Randomized Phase II Trial of Parsatuzumab (AntiâEGFL7) or Placebo in Combination with FOLFOX and Bevacizumab for FirstâLine Metastatic Colorectal Cancer
LESSONS LEARNED. These negative phase II results for parsatuzumab highlight the challenges of developing an agent intended to enhance the efficacy of vascular endothelial growth factor inhibition without the benefit of validated pharmacodynamic biomarkers or strong predictive biomarker hypotheses. Any further clinical development of antiâEGFL7 is likely to require new mechanistic insights and biomarker development for antiangiogenic agents. BACKGROUND. EGFL7 (epidermal growth factorâlike domain 7) is a tumorâenriched vascular extracellular matrix protein that supports endothelial cell survival. This phase II trial evaluated the efficacy of parsatuzumab (also known as MEGF0444A), a humanized antiâEGFL7 IgG(1) monoclonal antibody, in combination with modified FOLFOX6 (mFOLFOX6) (folinic acid, 5âfluorouracil, and oxaliplatin) bevacizumab in patients with previously untreated metastatic colorectal cancer (mCRC). METHODS. Oneâhundred twentyâseven patients were randomly assigned to parsatuzumab, 400 mg, or placebo, in combination with mFOLFOX6 plus bevacizumab, 5 mg/kg. Treatment cycles were repeated every 2 weeks until disease progression or unacceptable toxicity for a maximum of 24 months, with the exception of oxaliplatin, which was administered for up to 8 cycles. RESULTS. The progressionâfree survival (PFS) hazard ratio was 1.17 (95% confidence interval [CI], 0.71â1.93; pâ=â.548). The median PFS was 12 months for the experimental arm versus 11.9 months for the control arm. The hazard ratio for overall survival was 0.97 (95% CI, 0.46â2.1; pâ=â.943). The overall response rate was 59% in the parsatuzumab arm and 64% in the placebo arm. The adverse event profile was similar in both arms. CONCLUSIONS. There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for firstâline mCRC