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HIV COM THER
HIV/AIDS
Framework programme: 5
Project number:
QLK2-CT-2000-01040
EC contribution: € 1 469 718
Duration: 36 months
Type: RS
Starting date: 1 October 2000
Graphic element Development and Testing of a Combined Anti-Retroviral, Immune, and Gene Therapy for Treatment of HIV Patients
Keywords: HIV treatment; gene therapy; immune therapy; T-helper cells; HAART; AIDS

Summary:

The overall aim of this project is to develop a new strategy for the treatment of HIV patients, based on a combination of gene therapy and immune therapy as a supplement or possible alternative for the anti-retroviral therapies currently being used.

Problem:

The treatment of HIV patients has been greatly improved by the development of HAART. However, despite a strong reduction in the number of virus producing cells, HAART does not fully eradicate the virus, making sustained treatment necessary. In addition, immune function is only partly restored during HAART. Therefore, the focus has recently shifted to supplementing HAART with additional immune therapy. Although the most direct immune therapy approach would be to vaccinate HIV-infected individuals, recent data obtained in humans, as well as in SIV-infected rhesus macaques, indicated that only limited responses can be achieved. Possibly this is because the immune system has not yet fully recovered at the time of immunisation. Alternatively, the activation of CD4 T-cells from the vaccination may increase their susceptibility to HIV infection, which, even in the presence of anti-retroviral therapy, could lead to clonal deletion instead of immune activation.

Aim:

The objective of this project is to systematically develop and test a novel approach for treating HIV patients, by using antigen-specific CD4 T-cells, amplified and genetically modified by retroviral transduction in vitro, in order to confer to them HIV resistance. Transfer of these cells, in combination with anti-retroviral drug therapy and vaccination strategies, will be used to boost the patient’s immune responses directed against HIV and common micro-organisms responsible for opportunistic infections.

Expected results:

  1. Establishing the capacity of antigen-specific T-cell lines, directed against HIV/SIV proteins and expanded ex vivo, to elicit a therapeutic anti-HIV/SIV response in vivo
  2. Establishing the capacity of transducing retroviral DNA constructs to inhibit HIV/SIV replication in CD4 T-cells in vitro and in vivo.
  3. Establishing the therapeutic potential of combining gene and immune therapy with drug treatment in a SIV/macaque preclinical model.

Potential applications:

The approach followed in this project allows for the potential of gene and immune therapy to be fully exploited for the treatment of HIV infected people. It is expected that this procedure will improve the single anti-retroviral drug therapy currently used, by further reducing the steady state virus load in the patient and/or lowering the drug dose required to suppress virus replication.

Coordinator:

G. Koopman
Biomedical Primate Research Centre
Lange Kleiweg 139
2288 GJ Rijswijk
The Netherlands
Tel: +31 15 284 2841
Fax: +31 15 284 3986
E-mail: koopman@bprc.nl

Partners:

Principal
Scientific
Participants
Official Address Other Information
2Balbino AlarcónConsejo Superior De Investigaciones Cientificas (CSIC)
Centro de Biología Molecular Severo Ochoa
Facultad de Ciencias
Cantoblanco
ES-28049, Madrid
Spain
Tel: +34 91 397 8458
Fax: +34 91 397 4799
E-mail: balarcon@cbm.uam.es
3Fabrizio MancaUnit of Retroviral Immunology
Advanced Biotechnology Centre
Largo Rosanna Benzi, 10
IT-16132 Genova
Italy
Tel: +39 0913 978 458
Fax: +39 0913 974 799
E-mail: manca@ermes.cba.unige.it
4Gerd SutterGSF - Institute of Molecular Virology
Trogerstrasse 4b
DE-81675 München
Germany
Tel: +49 89 4140 7441
Fax: +49 89 4140 7444
E-mail: sutter@gsf.de
5Rosario CospedalGnomica S.A.U.
Alcarria 7
Pol. Industrial Coslada
ES-28760 Coslada, Madrid
Spain
Tel: +34 91 674 8990
Fax: +34 91 674 8991
E-mail: rcospedal@genomica.es
6Karen Willard-GalloLaboratoire d' Hématologie Experimentale
Université Libre de Bruxelles (ULB)
Blvd. de Waterloo, 121
BE-1000 Bruxelles
Belgium
Tel: +32 2 541 3739
Fax: +32 2 541 3453
E-mail: kwillard@ulb.ac.be
7Dorothee von LaerGeorg-Speyer-Haus Infektionsbiologie
Paul-Ehrlich-Strasse 42-44
60596 Frankfurt
Germany
Tel: +49 172 4069569
Fax: +49 9 63395297
E-mail: laer@em.uni-frankfurt.de

 
 
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