Research output per year
Research output per year
Roeland Lameris, Adam Shahine, Daniel G. Pellicci, Adam P. Uldrich, Stephanie Gras, Jérôme Le Nours, Richard W.J. Groen, Jana Vree, Scott J.J. Reddiex, Sergio M. Quiñones-Parra, Stewart K. Richardson, Amy R. Howell, Sonja Zweegman, Dale I. Godfrey, Tanja D. de Gruijl, Jamie Rossjohn, Hans J. van der Vliet
Research output: Contribution to journal › Article › Research › peer-review
Antibody-mediated modulation of major histocompatibility complex (MHC) molecules, or MHC class I-like molecules, could constitute an effective immunotherapeutic approach. We describe how single-domain antibodies (VHH), specific for the human MHC class I-like molecule CD1d, can modulate the function of CD1d-restricted T cells and how one VHH (1D12) specifically induced strong type I natural killer T (NKT) cell activation. The crystal structure of the VHH1D12-CD1d(α-GalCer)-NKT T-cell receptor (TCR) complex revealed that VHH1D12 simultaneously contacted CD1d and the type I NKT TCR, thereby stabilizing this interaction through intrinsic bispecificity. This led to greatly enhanced type I NKT cell-mediated antitumor activity in in vitro, including multiple myeloma and acute myeloid leukemia patient-derived bone marrow samples, and in vivo models. Our findings underscore the versatility of VHH molecules in targeting composite epitopes, in this case consisting of a complexed monomorphic antigen-presenting molecule and an invariant TCR, and represent a generalizable antitumor approach.
Original language | English |
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Pages (from-to) | 1054-1065 |
Number of pages | 12 |
Journal | Nature Cancer |
Volume | 1 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2020 |
Research output: Other contribution › Other
Research output: Contribution to journal › Creative Work › Other
Whisstock, J. (Primary Chief Investigator (PCI)), Abbey, B. (Chief Investigator (CI)), Nugent, K. A. (Chief Investigator (CI)), Quiney, H. M. (Chief Investigator (CI)), Godfrey, D. I. (Chief Investigator (CI)), Heath, W. (Chief Investigator (CI)), Fairlie, D. P. (Chief Investigator (CI)), Chapman, H. (Partner Investigator (PI)), Peele, A. (Partner Investigator (PI)), Davey, J. (Partner Investigator (PI)) & Wittmann, A. (Project Manager)
30/06/14 → 31/03/21
Project: Research
15/09/20
1 Media contribution
Press/Media: Expert Comment
Shahine, A. (Recipient), 2021
Prize: Prize (including medals and awards)
Facility/equipment: Facility
Kong, G. (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility