Abstract

DAB389IL-2 is an interleukin-2 receptor (IL-2R) specific fusion protein produced by recombinant DNA techniques by expression of a fusion gene in E. coli. The fusion gene consists of nucleotide sequences for the enzymatically active and membrane translocation domains of diphtheria toxin together with sequences for human interleukin-2 (IL-2). DAB389IL2 is specifically cytotoxic for cells bearing high-affinity IL-2R. The purspose of this study is to explore an in vivo dose-response relationship between administration of DAB389IL-2 and cell death in susceptible immune cells. Once the kinetics of activated T-cell death and re-population are established, this information may be used to help determine dose levels and treatment intervals for actual clinical use. This protocol is intended to establish proof-of-concept for the assays and methods used to measure these parameters. These assays have the potential to determine a dose-response relationship between different dosing schedules of DAB389IL-2 and the cytotoxicity and repopulation of specific T-lymphocyte subsets may provide a potential basis for the selection of dosing intervals and frequencies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000102-35
Application #
6277141
Study Section
Project Start
1997-12-01
Project End
1999-11-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
35
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

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Ansar, Muhammad; Raza, Syed Irfan; Lee, Kwanghyuk et al. (2015) A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair. J Med Genet 52:676-80
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Rosenbaum, Michael; Leibel, Rudolph L (2014) 20 years of leptin: role of leptin in energy homeostasis in humans. J Endocrinol 223:T83-96
Barbuto, Scott; Idoyaga, Juliana; Vila-Perelló, Miquel et al. (2013) Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells. Nat Chem Biol 9:250-6
Guo, Xiuyang; Dhodapkar, Kavita M (2012) Central and overlapping role of Cathepsin B and inflammasome adaptor ASC in antigen presenting function of human dendritic cells. Hum Immunol 73:871-8
Dustin, Lynn B; Charles, Edgar D (2012) Primary, post-primary and non-specific immunoglobulin M responses in HCV infection. Antivir Ther 17:1449-52
Pendyala, Swaroop; Walker, Jeanne M; Holt, Peter R (2012) A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology 142:1100-1101.e2

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