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In vivo cervical cancer growth inhibition by genetically engineered cytotoxic T cells

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Abstract

Purpose: The CD44 v7/8 splice variant that is frequently expressed in cervical carcinoma and rarely expressed in normal tissues displays promising properties as a target antigen for cancer immune therapy. In this study, cytotoxic T lymphocytes (CTLs) were genetically engineered to gain CD44v7/8 target specificity. Methods: Clone 96 (CI96), an established murine cytotoxic T-cell line, and naïve murine T cells were retrovirally transduced with a fusion gene construct encoding for the single chain fragment scFv of the monoclonal antibody VFF17 and for the ζ chain of the T-cell receptor (TCR). The therapeutic potential of genetically engineered T cells was tested in vitro and in vivo. Results: Surface expression of the chimeric TCR on infected Cl96 and naïve T cells was shown by FACS analysis. CD44v7/8-positive target cells were efficiently lysed by transduced Cl96 and naïve T cells, demonstrating the functionality and specificity of the chimeric TCR. In a xenograft BALB/c mouse model, efficient growth retardation of CD44v7/8-positive tumours was mediated by genetically engineered Cl96(VFF17)cyYZ cells. Conclusions: We were able to reprogramme the target specificity of recombinant Cl96 and naïve CTLs resulting in efficient cytolysis of CD44v7/8-positive cervical cancer cells. High transduction rates and the specific cytolysis of CD44v7/8-redirected CTLs are promising tools for an immune gene therapy approach for advanced cervical cancer.

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Abbreviations

Ab:

Antibody

CTL:

Cytolytic T lymphocyte

mAb:

Monoclonal antibody

TCR:

T-cell receptor

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Authors and Affiliations

  1. Department of Obstetrics/Gynaecology, University of Duesseldorf Medical Center, Moorenstrasse 5, 40225, Duesseldorf, Germany

    Peter Dall, Isabell Herrmann, Bettina Durst, Mariam A. Stoff-Khalili, Gerd Bauerschmitz, Bettina Hanstein & Dieter Niederacher

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  1. Peter Dall
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  2. Isabell Herrmann
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  3. Bettina Durst
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Correspondence to Peter Dall.

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Dall, P., Herrmann, I., Durst, B. et al. In vivo cervical cancer growth inhibition by genetically engineered cytotoxic T cells. Cancer Immunol Immunother 54, 51–60 (2005). https://doi.org/10.1007/s00262-004-0569-x

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