Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    TCR's genetically linked to CD28 and CD3e do not mispair with endogous TCR chains and mediate enhanced T cell persistance and anti-melanoma activity
    Govers, C.C.F.M. ; Sebestyen, Z. ; Roszik, J. ; Brakel, M. van; Berrevoets, C. ; Szoor, A. ; Panoutsopoulou, K. ; Broertjes, M. ; Van, T. ; Vereb, G. ; Szollosi, J. ; Debets, R. - \ 2014
    The Journal of Immunology 193 (2014)10. - ISSN 0022-1767 - p. 5315 - 5326.
    chimeric-antigen-receptor - gene-transfer - metastatic melanoma - cancer regression - lymphocytes - therapy - alpha - activation - toxicity - survival
    Adoptive transfer of T cells that are gene engineered to express a defined TCR represents a feasible and promising therapy for patients with tumors. However, TCR gene therapy is hindered by the transient presence and effectiveness of transferred T cells, which are anticipated to be improved by adequate T cell costimulation. In this article, we report the identification and characterization of a novel two-chain TCR linked to CD28 and CD3e (i.e., TCR:28e). This modified TCR demonstrates enhanced binding of peptide–MHC and mediates enhanced T cell function following stimulation with peptide compared with wild-type TCR. Surface expression of TCR:28e depends on the transmembrane domain of CD28, whereas T cell functions depend on the intracellular domains of both CD28 and CD3e, with IL-2 production showing dependency on CD28:LCK binding. TCR:28e, but not wild-type TCR, induces detectable immune synapses in primary human T cells, and such immune synapses show significantly enhanced accumulation of TCR transgenes and markers of early TCR signaling, such as phosphorylated LCK and ERK. Importantly, TCR:28e does not show signs of off-target recognition, as evidenced by lack of TCR mispairing, as well as preserved specificity. Notably, when testing TCR:28e in immune-competent mice, we observed a drastic increase in T cell survival, which was accompanied by regression of large melanomas with limited recurrence. Our data argue that TCR transgenes that contain CD28, and, thereby, may provide T cell costimulation in an immune-suppressive environment, represent candidate receptors to treat patients with tumors.
    Magnetic-Activated Cell Sorting of TCR-engineered T cells using tCD34 as a gene marker, but not peptide-MHC multimers, results in significant numbers of functional CD4 and CD8 T cells
    Govers, C. ; Berrevoets, C. ; Treffers-Westerlaken, E. ; Broertjes, M. ; Debets, R. - \ 2012
    Human Gene Therapy Methods 23 (2012)3. - ISSN 1946-6536 - p. 213 - 224.
    adoptive transfer - metastatic melanoma - cancer regression - immune-responses - lymphocytes-t - antigen - therapy - generation - receptors - requires
    T cell sorting technologies with peptide-MHC multimers or antibodies against gene markers enable enrichment of antigen-specific T cells and are expected to enhance therapeutic efficacy of clinical T cell therapy. However, a direct comparison between sorting reagents for their ability to enrich T cells is lacking. Here, we compared the in vitro properties of primary human T cells gene-engineered with gp100280-288/HLA-A2 specific TCRaß upon Magnetic Activated Cell Sorting (MACS) with different peptide-MHC multimers or an antibody against truncated CD34 (tCD34). With respect to peptide-MHC multimers, we observed that streptamers, when compared to pentamers and tetramers, improved T cell yield as well as level and stability of enrichment of TCR-engineered T cells (> 65% of peptide-MHC-binding T cells, stable for at least 6 weeks). In agreement with these findings, streptamers, the only detachable reagent, revealed significant T cell expansion in the 1st week after MACS. Sorting TCR and tCD34 gene-engineered T cells with CD34 mAb resulted in the most significant T cell yield and enrichment of T cells (> 95% of tCD34 T cells, stable for at least 6 weeks). Notably, T cells sorted with CD34 mAb, when compared to streptamer, bind about two to three-fold less peptide-MHC but show superior antigen-specific up-regulated expression of CD107a and production of IFN¿. Multi-parameter flow cytometry revealed that CD4 T cells, uniquely present in CD34 mAb-sorted T cells, contributed to enhanced IFN¿ production. Taken together, we postulate that CD34 mAb-based sorting of gene-marked T cells has benefits towards applications of T cell therapy, especially those that require CD4 T cells.
    Moisture content development in lap-joints of different wood species in outside exposure trials.
    Militz, H. ; Broertjes, M. ; Bloom, C.J. - \ 1998
    In: 29th Annual meeting of the Int. Research Group on Wood Preservation, Maastricht, The Netherlands (1998)
    Leerbare natuur- en milieu-educatie. Lezing door A. Alblas.
    Alblas, A. ; Broertjes, J. ; Janssen, F. ; Waarlo, A.J. - \ 1995
    In: Caring for the earth: de betekenis voor nme / de Lange, O., - p. 17 - 24.
    Praktijk-theorie en theorie over de ontwikkeling van betrokkenheid bij de natuur.
    Janssen, F.J.J.M. ; Waarlo, A.J. ; Alblas, A.H. ; Broertjes, J.J.S. - \ 1994
    Pedagogische Studiën 71 (1994). - ISSN 0165-0645 - p. 200 - 208.
    Praktisches Wissen und theoretische Erkenntnisse über Lernprozesse im Bereich der Natur- und Umweltbildung.
    Janssen, F. ; Waarlo, A.J. ; Alblas, A. ; Broertjes, J. - \ 1993
    In: Umweltbildung und Schulreform / Stokking, K., Ilien, A., Univ. Hannover (Fachbereich Erziehungswissenschaften 1) - p. 170 - 193.
    Praktijkkennis van leraren over natuur- en milieu-educatieve leerprocessen.
    Alblas, A.H. ; Broertjes, J. ; Janssen, F.J.J.M. ; Waarlo, A.J.W. - \ 1993
    In: Proc. Onderwijsresearchdagen, H. van Berkel et al. (red.). Bohn Stafleu Van Loghum, Houten/Zaventem (1993) 107
    Begrip en betrokkenheid. Bouwstenen voor leerbare thema's in natuur- en milieu-educatie.
    Alblas, A.H. ; Broertjes, J.J.S. ; Janssen, F.J.J.M. ; Waarlo, A.J. - \ 1993
    Wageningen [etc.] : Vakgroep Agrarische Onderwijskunde, Landbouwuniversiteit Wageningen [etc.] - ISBN 9789067542944 - 104 p.
    Obituary Cornelis Broertjes (1924-1991).
    Harten, A.M. van - \ 1992
    Mutation Breeding Newsletter 39 (1992)1/2.
    The present state of mutation breeding in vegetatively propagated crops.
    Harten, A.M. ; Broertjes, C. - \ 1991
    In: Advances in plant breeding, Vol. 1 / Mandal, A.K., - p. 221 - 227.
    Induced mutations in vegetatively propagated crops.
    Harten, A.M. van; Broertjes, C. - \ 1989
    In: Plant breeding reviews 6 / Janick, J., - p. 55 - 90.
    Applied mutation breeding for vegetatively propagated crops.
    Broertjes, C. ; Harten, A.M. van - \ 1988
    Amsterdam : Elsevier (Developments in crop science 12) - ISBN 9780444427861 - 345
    mutaties - plantenveredeling - vegetatieve vermeerdering - mutations - plant breeding - vegetative propagation
    Application of mutation breeding methods to vegetatively propagated plants.
    Broertjes, C. ; Harten, A.M. van - \ 1987
    In: Improving vegetatively propagated crops / Abbott, A.J., Atkin, R.K., London : Academic Press - p. 335 - 348.
    Sporten, mutanten en somaklonale varianten.
    Broertjes, C. ; Harten, A.M. van - \ 1986
    Vakblad voor de Bloemisterij 44 (1986). - ISSN 0042-2223 - p. 61 - 61.
    Mutation breeding: a stepping-stone between Gregor Mendel and genetic manipulation (a treatise for vegetatively propagated crops).
    Harten, A.M. van; Broertjes, C. - \ 1986
    In: Genetic manipulation in plant breeding : proceedings international symposium organized by Eucarpia, september 8 - 13, 1985, Berlin (West), Germany. - Berlin : Gruyter - ISBN 9783110105964 - p. 3 - 15.
    Single cell origin of adventitious buds
    Broertjes, C. ; Harten, A.M. van - \ 1985
    Euphytica 34 (1985). - ISSN 0014-2336 - p. 93 - 95.
    Enige resultaten van een geohydrologisch onderzoek in het zuidelijk Peelgebied
    Rees Vellinga, E. van; Broertjes, J.P. - \ 1984
    Wageningen : ICW (Nota / Instituut voor Cultuurtechniek en Waterhuishouding 1590) - 17
    watervoerende lagen - permeabiliteit - nederland - de peel - pompproeven - aquifers - permeability - maps - de peel - pumping tests
    In het zuidelijk Peelgebied wordt door een multidisciplinaire projectgroep een onderzoek verricht tot ontwikkeling van een procedure waarmee alternatieven voor het beheer van grond- en oppervlaktewater kunnen worden geanalyseerd en geëvalueerd, zowel met betrekking tot de waterkwaliteit als de -kwantiteit, in regio's waar landbouw, natuur en openbare watervoorziening belangrijke en dikwijls tegengestelde belangen hebben.
    Verslag van een bezoek aan enkele Westduitse onderzoekinstellingen : van 17 - 20 oktober 1983
    Nieuwhof, M. ; Broertjes, C. - \ 1983
    Wageningen : IVT (Rapport / Instituut voor de Veredeling van Tuinbouwgewassen no. 188)
    proefstations - bondsrepubliek duitsland - plantenveredeling - onderzoeksinstituten - experimental stations - german federal republic - plant breeding - research institutes
    Verslag van een reis naar Schotland en Engeland : augustus / september 1982
    Broertjes, C. ; Eijk, J.P. van; Tuyl, J.M. van - \ 1982
    Wageningen : I.V.T. (Rapport / Instituut voor de Veredeling van Tuinbouwgewassen no. 176) - 10
    groot-brittannië - tuinbouw - plantenveredeling - plantenziekten - afwijkingen, planten - plantenziektekunde - plantenplagen - gewasbescherming - great britain - horticulture - plant breeding - plant diseases - plant disorders - plant pathology - plant pests - plant protection
    Analysis of mitochondrial and chloroplast DNA from fertile and cytoplasmic male-sterile Petunia hybrida
    Kool, A.J. ; Haas, J.M. de; Marrewijk, G.A.M. van - \ 1982
    In: Induced variability in plant breeding / Broertjes, C., Wageningen : Pudoc - p. 127 - 127.
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