Council News Vol. 7, no. 2

Therapy of HIV with Genetically Modified T-Cell Clones
Philip Greenberg, Fred Hutchinson Cancer Research Center
Performing both preclinical and pilot clinical studies, the investigators of this renewal
SPIRAT grant are developing and testing strategies for establishing an effective T-cell
response to HIV-1. They will accomplish this by using adoptive transfer of autologous,
HIV-specific CD8+ and CD4+ T-cell clones and will monitor the effects on virus
reservoirs and viral diversity.

Project 1 Dr. Stanley
Riddell, FHCRC
Treatment of HIV with
Gene-Modified CD8+ TCell Clones

Project 2 Dr. Philip
Greenberg, FHCRC
Transfer of HIV-Specific
CD4+ T-Cell Clones with
Genes Inhibiting HIV

Project 3 Dr. James
Mullins, University of
Washington
Impact of T-Cell Therapy on
HIV Population Dynamics

Combination Genetic and Immune Therapies for AIDS
Gary Nabel, University of Michigan
Dr. Nabel's lab will use molecular genetic and other strategies to inhibit viral replication
and optimize immune function in HIV-infected children and adults. For this renewal
SPIRAT grant, the group continues to study the RevMlO antiviral gene and develop new
antiviral vectors targeting virus and host factors, including chemokine receptors. New
emphases are the transduction of hematopoietic stem cells, in addition to mature T cells,
in clinical studies and the analysis of immune responses to vectors and recombinant
genes in transduced cells.

Project 1 Dr. Gary Nabel,
University of Michigan
Combination Gene Transfer, Antiviral Treatment,
and Immunostimulation
for HIV Infection
Project 2 Dr. Donald
Kohn

Children's Hospital, Los
Angeles
Hematopoietic Stem Cells
for Gene Therapy with
RevMlO
Project 3 Dr. Garry Nolan,
Stanford University
Safe Lentiviral Vectors for

Gene Transfer to Nondividing Cells
Project 4 Dr. Daniel
Littman, New York
University
Chemokine Receptor
Intervention Using Gene
Therapy and Animal Models

Novel HIV Therapies: IPCP
Ellis Reinherz, Dana-Farber Cancer Institute
In this second renewal, the investigators will continue studying the structural biology of
CD4-HIV-1 envelope interaction as a basis for rational drug discovery. This work follows
their elucidation of the atomic structure of two-domain CD4 under the original grant and
identification of CD4 amino acid residues that are binding sites in CD4-gp120 and CD4 -MHC class II interactions. The new proposal will use x-ray crystallography and nuclear
magnetic resonance to search for peptides that interfere with CD4-gpl20 binding.
Project 1 Dr. Ellis Project 2 Dr. Stephen Project 3 Dr. Gerhard
Reinherz, Dana-Farber Harrison, Children's Wagner, Harvard Medical
Cancer Institute Hospital, Boston School

Structural Analysis of
CD4-Ligand Interaction

Structural Biology of HIV
Envelope Interactions

NMR-Based Discovery of
HIV Inhibitors

Novel H IV Therapies-continued on page 19