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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1791-1795. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-09-3023. This Article Full Text (PDF) All Versions of this Article: 2003-09-3023v1 103/5/1791    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Stebbing, J. Articles by Savage, P. Search for Related Content PubMed PubMed Citation Articles by Stebbing, J. Articles by Savage, P. Social Bookmarking                   What's this? Submitted September 3, 2003 Accepted October 24, 2003 Antibody targeted MHC complex directed expansion of HIV-1 and KSHV-specific CD8 positive lymphocytes: a new approach to therapeutic vaccination Justin Stebbing, Brian Gazzard, Steve Patterson, Mark Bower, Dhayaneethie Perumal, Mark Nelson, Andrew McMichael, Graham Ogg, Agamemnon Epenetos, Frances Gotch, and Philip Savage* Department of Immunology, Chelsea and Westminster Hospital, London, United Kingdom; Departments of HIV Medicine and Oncology, Chelsea and Westminster Hospital, London, United Kingdom Immunology Group, Weatherall Institute, Oxford, United Kingdom Alexis Biotech, London, United Kingdom Department of Oncology, Velindre Hospital, Cardiff, United Kingdom * Corresponding author; email: Philip.Savage{at}velindre.tr.wales.nhs.uk. The ability of therapeutic vaccines to generate large numbers of CD8 positive T lymphocytes that have specificity for HIV-1 or other virally infected cells has enormous potential clinical value. However approaches to produce CTLs in vivo via vaccine technology have thus far been disappointing and the ex vivo production of cells for adoptive transfer is labour intensive and expensive. We describe the results of a two step antibody targeting system for the production of CD8 positive T lymphocytes specific for HIV-1 and Kaposi's sarcoma-associated herpesvirus (KSHV), suitable for use in vivo. In 8 consecutive HLA-A2 positive HIV-1 infected individuals with Kaposi's sarcoma, two cycles of this system resulted in greater than 1 Log increases of specific anti-HIV and anti-KSHV CD8 positive lymphocytes. These expanded cells have an effector phenotype which includes the ability to produce interferon- and CD45Ra+/CD69+ staining. We have shown that antibody targeted B cells can function as effective antigen presenting molecules and lead to sustained specific T lymphocyte expansion from PBMCs of immunosuppressed individuals. This approach, which offers an easy and effective protocol for the amplification of specific anti-viral and anti-tumour CTLs, may offer significant advances for in vivo T cell immunotherapeutic protocols. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Stebbing, A. Sanitt, A. Teague, T. Powles, M. Nelson, B. Gazzard, and M. Bower Prognostic Significance of Immune Subset Measurement in Individuals With AIDS-Associated Kaposi's Sarcoma J. Clin. Oncol., June 1, 2007; 25(16): 2230 - 2235. [Abstract] [Full Text] [PDF] V. Cesson, K. Stirnemann, B. Robert, I. Luescher, T. Filleron, G. Corradin, J.-P. Mach, and A. Donda Active Antiviral T-Lymphocyte Response Can Be Redirected against Tumor Cells by Antitumor Antibody x MHC/Viral Peptide Conjugates Clin. Cancer Res., December 15, 2006; 12(24): 7422 - 7430. [Abstract] [Full Text] [PDF] M. Bower, N. McCall-Peat, N. Ryan, L. Davies, A. M. Young, S. Gupta, M. Nelson, B. Gazzard, and J. Stebbing Protease inhibitors potentiate chemotherapy-induced neutropenia Blood, November 1, 2004; 104(9): 2943 - 2946. [Abstract] [Full Text] [PDF]

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