• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Tebentafusp, a TCR/anti-CD3 bispecific fusion protein targeting gp100, potently activated anti-tumor immune responses in patients with metastatic melanoma

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Middleton, M. R.
    McAlpine, C.
    Woodcock, V. K.
    Corrie, P.
    Infante, J. R.
    Steven, N. M.
    Evans, T. R. J.
    Anthoney, A.
    Shoushtari, A. N.
    Hamid, O.
    Gupta, Avinash
    Vardeu, A.
    Leach, E.
    Naidoo, R.
    Stanhope, S.
    Lewis, S. M.
    Hurst, J.
    O'Kelly, I.
    Sznol, M.
    Show allShow less
    Affiliation
    Oncology, University of Oxford
    Issue Date
    2020
    
    Metadata
    Show full item record
    Abstract
    Purpose: Tebentafusp is a first-in-class bispecific fusion protein designed to target gp100 (a melanoma-associated antigen) through a high affinity T cell receptor binding domain, and an anti-CD3 T cell engaging domain which redirects T cells to kill gp100-expressing tumor cells. Here we report from a multicentre Phase 1/2 trial of tebentafusp in metastatic melanoma (NCT01211262) focusing on the mechanism of action of tebentafusp Experimental Design: 84 patients with advanced melanoma received tebentafusp. Treatment efficacy, treatment-related AEs and biomarker assessments were performed for blood-derived and tumor biopsy samples obtained at baseline and on-treatment Results: Tebentafusp was generally well tolerated and active in both metastatic uveal melanoma (mUM) and metastatic cutaneous melanoma (mCM) patients. A 65% 1-year overall survival rate was achieved for both patient cohorts. On-treatment cytokine measurements were consistent with the induction of IFNg pathway-related markers in the periphery and tumor. Notably, tebentafusp induced an increase in serum CXCL10 (a T cell attractant), and a reduction in circulating CXCR3+ CD8+ T cells together with an increase in cytotoxic T cells in the tumor microenvironment. Furthermore, increased serum CXCL10 or the appearance of rash, (likely due to cytotoxic T cells targeting of gp100-expressing skin melanocytes) showed a positive association with patient survival. Conclusions: These data suggest that re-directing T cells using a gp100-targeting T cell receptor/anti-CD3 bispecific fusion protein may provide benefit to patients with metastatic melanoma. Furthermore, the activity observed in these two molecularly disparate melanoma classes hints at the broad therapeutic potential of tebentafusp.
    Citation
    Middleton MR, McAlpine C, Woodcock VK, Corrie P, Infante JR, Steven NM, et al. Tebentafusp, a TCR/anti-CD3 bispecific fusion protein targeting gp100, potently activated anti-tumor immune responses in patients with metastatic melanoma. Clin Cancer Res. 2020.
    Journal
    Clinical Cancer Research
    URI
    http://hdl.handle.net/10541/623266
    DOI
    10.1158/1078-0432.ccr-20-1247
    PubMed ID
    32816891
    Additional Links
    https://dx.doi.org/10.1158/1078-0432.ccr-20-1247
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.ccr-20-1247
    Scopus Count
    Collections
    All Christie Publications

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.