Abstract

""""""""Dr. Waldmann's studies have focused on the role played by the IL-2-IL-2 receptor system in normal and abnormal T-cell function and the use of these insights to develop IL-2R directed therapy for leukemia. As part of his study of HTLV-I-associated adult T-cell leukemia (ATL), Dr. Waldmann, co-discovered a cytokine, IL-15, that stimulates T-cell proliferation and NK cell development. Dr. Waldmann showed that IL-15 message includes a number of elements that are impediments to its translation. In particular, the 5' UTR of the normal human IL-15 message is burdened with 10 upstream AUGs that interfere with efficient IL-15 translation. Furthermore, the unusually long 48 amino acid leader sequence and a cis- acting element in the 3' mature protein coding region interfere with this process. As a hypothesis he proposed that by maintaining a pool of translationally inactive IL-15 mRNA cells can readily respond to an intracellular infection by unburdening the IL-15 message transforming it into one that can be effectively translated.""""""""

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC004002-29
Application #
6123641
Study Section
Metabolism Study Section (MET)
Project Start
Project End
Budget Start
Budget End
Support Year
29
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Yu, P; Petrus, M N; Ju, W et al. (2015) Augmented efficacy with the combination of blockade of the Notch-1 pathway, bortezomib and romidepsin in a murine MT-1 adult T-cell leukemia model. Leukemia 29:556-66
Chen, Jing; Zhang, Meili; Ju, Wei et al. (2009) Effective treatment of a murine model of adult T-cell leukemia using depsipeptide and its combination with unmodified daclizumab directed toward CD25. Blood 113:1287-93
O'Mahony, Deirdre; Morris, John C; Stetler-Stevenson, Maryalice et al. (2009) EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with T-cell malignancies. Clin Cancer Res 15:2514-22
Pise-Masison, Cynthia A; Radonovich, Michael; Dohoney, Kathleen et al. (2009) Gene expression profiling of ATL patients: compilation of disease-related genes and evidence for TCF4 involvement in BIRC5 gene expression and cell viability. Blood 113:4016-26
O'Mahony, Deirdre; Morris, John C; Quinn, Cate et al. (2007) A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy. Clin Cancer Res 13:958-64
Bene, Laszlo; Kanyari, Zsolt; Bodnar, Andrea et al. (2007) Colorectal carcinoma rearranges cell surface protein topology and density in CD4+ T cells. Biochem Biophys Res Commun 361:202-7
Waldmann, T A (2007) Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma. Oncogene 26:3699-703
Sato, Noriko; Patel, Hiral J; Waldmann, Thomas A et al. (2007) The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells. Proc Natl Acad Sci U S A 104:588-93
Waldmann, Thomas A (2007) Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol 27:1-18
Perera, Liyanage P; Waldmann, Thomas A; Mosca, Joseph D et al. (2007) Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice. J Virol 81:8774-83

Showing the most recent 10 out of 56 publications