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de Bruin RCG, Veluchamy JP, Lougheed SM, et al. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells. Oncoimmunology. 2017;7(1):e1375641doi: 10.1080/2162402X.2017.1375641.
de Bruin, R. C. G., Veluchamy, J. P., Lougheed, S. M., Schneiders, F. L., Lopez-Lastra, S., Lameris, R., Stam, A. G., Sebestyen, Z., Kuball, J., Molthoff, C. F. M., Hooijberg, E., Roovers, R. C., Santo, J. P. D., van Bergen En Henegouwen, P. M. P., Verheul, H. M. W., de Gruijl, T. D., & van der Vliet, H. J. (2017). A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells. Oncoimmunology, 7(1), e1375641. https://doi.org/10.1080/2162402X.2017.1375641
de Bruin, Renée C G, et al. "A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells." Oncoimmunology vol. 7,1 (2017): e1375641. doi: https://doi.org/10.1080/2162402X.2017.1375641
de Bruin RCG, Veluchamy JP, Lougheed SM, Schneiders FL, Lopez-Lastra S, Lameris R, Stam AG, Sebestyen Z, Kuball J, Molthoff CFM, Hooijberg E, Roovers RC, Santo JPD, van Bergen En Henegouwen PMP, Verheul HMW, de Gruijl TD, van der Vliet HJ. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells. Oncoimmunology. 2017 Oct 20;7(1):e1375641. doi: 10.1080/2162402X.2017.1375641. eCollection 2017. PMID: 29296532; PMCID: PMC5739573.
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Oncoimmunology. 2017 Oct 20;7(1):e1375641. doi: 10.1080/2162402X.2017.1375641. eCollection 2017.

A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells.

Oncoimmunology

Renée C G de Bruin, John P Veluchamy, Sinéad M Lougheed, Famke L Schneiders, Silvia Lopez-Lastra, Roeland Lameris, Anita G Stam, Zsolt Sebestyen, Jürgen Kuball, Carla F M Molthoff, Erik Hooijberg, Rob C Roovers, James P Di Santo, Paul M P van Bergen En Henegouwen, Henk M W Verheul, Tanja D de Gruijl, Hans J van der Vliet

Affiliations

  1. Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
  2. Innate Immunity Unit, Institut Pasteur, Paris, France.
  3. Institut National de la Santé et de la Recherche Médicale (INSERM) U1223, Paris, France.
  4. Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
  5. Department of Hematology and Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
  6. Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
  7. Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
  8. Department of Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.

PMID: 29296532 PMCID: PMC5739573 DOI: 10.1080/2162402X.2017.1375641

Abstract

Though Vγ9Vδ2-T cells constitute only a small fraction of the total T cell population in human peripheral blood, they play a vital role in tumor defense and are therefore of major interest to explore for cancer immunotherapy. Vγ9Vδ2-T cell-based cancer immunotherapeutic approaches developed so far have been generally well tolerated and were able to induce significant clinical responses. However, overall results were inconsistent, possibly due to the fact that these strategies induced systemic activation of Vγ9Vδ2-T cells without preferential accumulation and targeted activation in the tumor. Here we show that a novel bispecific nanobody-based construct targeting both Vγ9Vδ2-T cells and EGFR induced potent Vγ9Vδ2-T cell activation and subsequent tumor cell lysis both

Keywords: EGFR; VHH; cancer; gamma delta T cells; immunotherapy; nanobody; single-domain antibody fragment; tumor

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