Abstract

) In this project we will test the concept of vaccination against a cell surface antigen expressed on normal as well as malignant B lymphocytes. We have chosen the CD20 molecule as the target of this effort because of its universal expression on Non Hodgkin's Lymphoma and because of our clinical success with passive antibody therapy against this molecule. We know from our work that B-cell depletion from passive antibody therapy in humans does not result in immunosuppression and from the work of others in knockout mice that the CD20 molecule is dispensable. The critical questions addressed by this proposal are therefore, can an immune response be induced against this autoantigen? If so, will such a response be deleterious to the host? And will an immune response against CD20 protect against the growth of B-cell lymphomas? The vaccine strategies will employ molecular constructs of the CD20 molecule both full length and the hydrophilic portions linked as fusion proteins to the cytosine Granulocyte Macrophage Colony Stimulating Factor, (G-CSF). These molecules will be presented to the immune system by Dendritic Cells (DC). In addition adenovirus (AdV) vectors will be constructed which express the CD20 molecule and these viruses will be tested as vaccines and as vectors for the delivery of the CD20 gene into dendritic cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA072103-05
Application #
6173325
Study Section
Special Emphasis Panel (SRC (20))
Program Officer
Forry-Schaudies, Suzanne L
Project Start
1996-09-30
Project End
2001-09-29
Budget Start
2000-09-30
Budget End
2001-09-29
Support Year
5
Fiscal Year
2000
Total Cost
$777,182
Indirect Cost

  Institution

Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Merad, Miriam; Sugie, Tomoharu; Engleman, Edgar G et al. (2002) In vivo manipulation of dendritic cells to induce therapeutic immunity. Blood 99:1676-82
Cantwell, M J; Wierda, W G; Lossos, I S et al. (2001) T cell activation following infection of primary follicle center lymphoma B cells with adenovirus encoding CD154. Leukemia 15:1451-7
Merad, M; Fong, L; Bogenberger, J et al. (2000) Differentiation of myeloid dendritic cells into CD8alpha-positive dendritic cells in vivo. Blood 96:1865-72
Brockstedt, D G; Podsakoff, G M; Fong, L et al. (1999) Induction of immunity to antigens expressed by recombinant adeno-associated virus depends on the route of administration. Clin Immunol 92:67-75