Preclinical assessment of CAR T-cell therapy targeting the tumor antigen 5T4 in ovarian cancer.
AuthorsOwens, Gemma L
Sheard, Victoria E
Cheadle, Eleanor J
Gilham, David E
AffiliationClinical and Experimental Immunotherapy Group, Department of Obstetrics and Gynaecology, Manchester Academic Health Science Centre, St Mary's Hospital, Central Manchester NHS Foundation Trust, Manchester
MetadataShow full item record
AbstractChimeric 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/.
CitationPreclinical assessment of CAR T-cell therapy targeting the tumor antigen 5T4 in ovarian cancer. 2017, J Immunother
JournalJournal of Immunotherapy
- 5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells.
- Authors: Guo X, Zheng H, Luo W, Zhang Q, Liu J, Yao K
- Issue date: 2017 Jul 7
- IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors <i>in vivo</i>.
- Authors: Koneru M, Purdon TJ, Spriggs D, Koneru S, Brentjens RJ
- Issue date: 2015 Mar
- Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen.
- Authors: Harrop R, O'Neill E, Stern PL
- Issue date: 2019
- Modification of cytokine-induced killer cells with folate receptor alpha (FRα)-specific chimeric antigen receptors enhances their antitumor immunity toward FRα-positive ovarian cancers.
- Authors: Zuo S, Wen Y, Panha H, Dai G, Wang L, Ren X, Fu K
- Issue date: 2017 May
- Effective Targeting of TAG72<sup>+</sup> Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells.
- Authors: Murad JP, Kozlowska AK, Lee HJ, Ramamurthy M, Chang WC, Yazaki P, Colcher D, Shively J, Cristea M, Forman SJ, Priceman SJ
- Issue date: 2018