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T-cell engineering by a chimeric T-cell receptor with antibody-type specificity for the HIV-1 gp120

Gene Therapy volume 12, pages 299–310 (2005)Cite this article

Abstract

Immune-based approaches of cell therapy against viral pathogens such as the human immunodeficiency virus type 1 (HIV-1) could be of primary importance for the control of this viral infection. Here, we designed a chimeric cell surface receptor (105TCR) to provide primary human T-lymphocytes with antibody-type specificity for the HIV-1 envelope glycoprotein. This receptor includes the single chain Fv domain of the neutralizing anti-gp120 human monoclonal antibody F105, CD8α hinge and the transmembrane and the cytoplasmic domains of TCRζ. Our results show that 105TCR is expressed at the cellular surface and is capable of recognizing the HIV-1 envelope glycoprotein inducing highly efficient effector T-cell responses, including extracellular signal-regulated kinase phosphorylation and cytokine secretion. Moreover, human primary CD8+ T-lymphocytes transduced by oncoretroviral and lentiviral vectors containing the 105TCR gene are able to mediate in vitro-specific cytolysis of envelope-expressing cells and HIV-1-infected CD4+ T-lymphocytes. These findings suggest that 105TCR is particularly suited for in vivo efficacy studies.

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Acknowledgements

We thank F Salandin for artwork. This work was supported by AIDS grants from the Istituto Superiore di Sanità (Rome-AIDS Projects no. 40D.64 to GP and no. 30D.60 to CP), the Fondazione Cassa di Risparmio di Padova e Rovigo, Regione Veneto, MIUR, FIRB, CNR Target Project on Biotechnology and AIRC.

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Authors and Affiliations

  1. Department of Histology, Microbiology and Medical Biotechnologies, Section of Microbiology and Virology, University of Padova, Padova, Italy

    S Masiero, C Del Vecchio, G Mattiuzzo, F Gennari, G Palù & C Parolin

  2. Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy

    R Gavioli

  3. Department of Molecular Biology, Virology Section, University of Siena, Siena, Italy

    M G Cusi & L Micheli

  4. Department of Biology and Genetics, University of Milano, Milano, Italy

    A Siccardi

  5. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA

    W A Marasco

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Masiero, S., Del Vecchio, C., Gavioli, R. et al. T-cell engineering by a chimeric T-cell receptor with antibody-type specificity for the HIV-1 gp120. Gene Ther 12, 299–310 (2005). https://doi.org/10.1038/sj.gt.3302413

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