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    Preclinical assessment of CAR T-cell therapy targeting the tumor antigen 5T4 in ovarian cancer.

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    Authors
    Owens, Gemma L
    Sheard, Victoria
    Kalaitsidou, Milena
    Blount, D
    Lad, Y
    Cheadle, Eleanor J
    Edmondson, R
    Kooner, G
    Gilham, David E
    Harrop, Richard
    Affiliation
    Clinical and Experimental Immunotherapy Group, Department of Obstetrics and Gynaecology, Manchester Academic Health Science Centre, St Mary's Hospital, Central Manchester NHS Foundation Trust, Manchester
    Issue Date
    2017-12-12
    
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    Abstract
    Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome both quantitative and qualitative shortfalls of the host immune system relating to the detection and subsequent destruction of tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step in the ability to utilize CAR T cells for the treatment of cancer. The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer. Matched blood and tumor samples were collected from 12 patients with ovarian cancer; all tumors were positive for 5T4 expression by immunohistochemistry. Patient T cells were effectively transduced with 2 different anti-5T4 CAR constructs which differed in their affinity for the target antigen. Co-culture of CAR T cells with matched autologous tumor disaggregates resulted in antigen-specific secretion of IFN-gamma. Furthermore, assessment of the efficacy of anti-5T4 CAR T cells in a mouse model resulted in therapeutic benefit against established ovarian tumors. These results demonstrate proof of principle that 5T4 is an attractive target for immune intervention in ovarian cancer and that patient T cells engineered to express a 5T4-specific CAR can recognize and respond physiologically to autologous tumor cells.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
    Citation
    Preclinical assessment of CAR T-cell therapy targeting the tumor antigen 5T4 in ovarian cancer. 2017, J Immunother
    Journal
    Journal of Immunotherapy
    URI
    http://hdl.handle.net/10541/620779
    DOI
    10.1097/CJI.0000000000000203
    PubMed ID
    29239915
    Type
    Article
    Language
    en
    ISSN
    1537-4513
    ae974a485f413a2113503eed53cd6c53
    10.1097/CJI.0000000000000203
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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