The keyword search here on SI must be loused up--I will refresh the topic one last time...
Here is the link to SPIRAT again
fhcrc.org
and the old Tgen PR
noonanrusso.com
(Nature Medicine...In vivo Migration and Function of Transferred HIV-1 Specific Cytotoxic T Cells)
A more recent paper without Tgen...
J Immunol 1999 Jul 15;163(2):861-7
The antiviral activity of HIV-specific CD8+ CTL clones is limited by elimination due to encounter with HIV-infected targets. McKinney DM, Lewinsohn DA, Riddell SR, Greenberg PD, Mosier DE
...sometimes FHCRC links stop working, so here is some
old stuff, from 1997, that was in the google cache...
Strategic Program for Innovative Research on AIDS Treatment (SPIRAT) Philip Greenberg, M.D., Stanley Riddell, M.D., Brad Nelson, Ph.D., Mark Gilbert, M.D. and Michael Emerman, Ph.D.
SPIRAT consists of six research teams, based primarily at the Hutchinson Center and University of Washington, to investigate ways to accelerate the development of innovative therapies to fight HIV infection. A primary focus of the Hutchinson Center teams is to concentrate on ways to bolster the immune system cells that are essential to mount an effective immune response against HIV. SPIRAT began in September 1994 and is funded by the National Institute of Allergy and Infectious Disease.
The team's efforts are divided into four research projects and two scientific cores that will form a collaborative enterprise between basic and clinical scientists. The projects are:
Project one: coordinated by Stanley Riddell, M.D., and Brad Nelson, Ph.D., at the Hutchinson Center, will focus on adoptive immunotherapy, which uses a participant's CD8+ T-cells (T-cells are the "killer" cells of the immune system) that specifically target HIV-infected cells. These cells are expanded to large quantities in the lab and genetically modified with a suicide gene (HyTK) vector (a modified virus that enables scientists to insert genetic changes within a cell), developed by Targeted Genetics Corporation, prior to reinfusion into the participant. Methods are being developed to enhance the effectiveness of the transferred cells by introducing additional genes into the cells.
Project two: coordinated by Mark Gilbert, M.D., and Philip Greenberg, M.D., at the Hutchinson Center, will focus on methods to reconstitute immunity by the adoptive transfer of CD4+ T-cells (known as the "helper" cells of the immune system) that have been isolated, expanded in tissue culture and genetically modified with genes that mediate an effect called intracellular immunization (IC-imm) (i.e. the modified cell is rendered resistant to HIV). Targeted Genetics Corporation is developing vectors which will inhibit the replication of HIV in the target cells. The primary goal is to determine strategies that can maintain or restore the immune function in HIV-infected individuals.
Project three: coordinated by Donald Mosier, Ph.D., M.D., at The Scripps Research Institute, will test the activity of the genetically modified CD8+ or CD4+ T-cells generated in projects one and two in a small-animal model. This will be done by injecting these cells into mice with severe combined immunodeficiency (SCID) that have been reconstituted with human immune systems and by challenging the mice with HIV.
Project four: coordinated by Michael Emerman, Ph.D., at the Hutchinson Center, will use a highly sensitive assay, known as polymerase chain reaction (PCR), to measure the relative level of activity of virus in infected cells. This information will be compared with classical markers of HIV activity in the participants enrolled in projects one and two. The measurements will be used to determine the number of cells that harbor latent (or dormant) viruses versus the number of cells that have active viruses.
The two scientific cores will provide virology and retroviral vectors to support the projects.
The virology core, coordinated by Lawrence Corey, M.D., at the Fred Hutchinson Cancer Research Center and the University of Washington, will perform the serologic and virologic studies required to screen participants for enrollment into projects one and two, as well as evaluate what effects the new therapies will have on inhibiting HIV replication in the host. They will also assay if resistance to the therapy occurs over time.
The retroviral vector core, coordinated by Barrie Carter, Ph.D., at Targeted Genetics Corporation (TGEN), will provide the clinical investigators at the Fred Hutchinson Cancer Research Center with services relating to generation, manufacturing and validation of clinical-grade vectors which will be used in project one and two. TGEN will handle all regulatory filings with the FDA relating to the manufacturing and clinical use of these vectors. |
