Abstract

Rheumatoid arthritis is an autoimmune disease associated w/the MHC Class II marker HLA-SR4. This observation and other data suggest an important pathogenic role for T cell-mediated presentation of an autoantigen in the context of HLA-DR4. Self-peptides which are presented to T cell receptors may perpetuate the aberrant immune response characteristic of this chronic disease. Intervention to induce selective energy or apoptosis of activated autoreactive T cells could have therapeutic benefit. The construct being tested utilizes a peptide derived from human cartilage glycoprotein 39 (Hcgp39) which induces arthritis in mice. Vaccination of individuals w/the appropriate MHC Class II marker complexed w/HCgp39 is proposed as a method for induction of specific immune unresponsiveness.
SPECIFIC AIMS : Patients w/RA will be treated w/the MHCII: Peptide complex containing Hcgp39 and DR4, designated AG4263, in a double blind, multicenter trial. The primary objective is to evaluate safety and tolerability of an induction course and one maintenance cycle of AG4263. The secondary objectives are to evaluate the biological effects of AG4263, to obtain pharmacokinetic data and to get a preliminary assessment of effects on disease activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000095-40
Application #
6409518
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
1977-12-01
Project End
2002-11-30
Budget Start
Budget End
Support Year
40
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203

  Publications

Kaltenbach, Karol; O'Grady, Kevin E; Heil, Sarah H et al. (2018) Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes. Drug Alcohol Depend 185:40-49
Gupta, Samir K; Yeh, Eunice; Kitch, Douglas W et al. (2017) Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s. J Antimicrob Chemother 72:2042-2048
Gilchuk, Pavlo; Knight, Frances C; Wilson, John T et al. (2017) Eliciting Epitope-Specific CD8+ T Cell Response by Immunization with Microbial Protein Antigens Formulated with ?-Galactosylceramide: Theory, Practice, and Protocols. Methods Mol Biol 1494:321-352
Sebag, Sara C; Koval, Olha M; Paschke, John D et al. (2017) Mitochondrial CaMKII inhibition in airway epithelium protects against allergic asthma. JCI Insight 2:e88297
Laird, Chris; Burdorf, Lars; Pierson 3rd, Richard N (2016) Lung xenotransplantation: a review. Curr Opin Organ Transplant 21:272-8
Chung, C P; Ormseth, M J; Connelly, M A et al. (2016) GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus. Lupus 25:296-300
Towse, Theodore F; Childs, Benjamin T; Sabin, Shea A et al. (2016) Comparison of muscle BOLD responses to arterial occlusion at 3 and 7 Tesla. Magn Reson Med 75:1333-40
Joy, Nino G; Mikeladze, Maia; Younk, Lisa M et al. (2016) Effects of equivalent sympathetic activation during hypoglycemia on endothelial function and pro-atherothrombotic balance in healthy individuals and obese standard treated type 2 diabetes. Metabolism 65:1695-1705
Gilchuk, Pavlo; Hill, Timothy M; Guy, Clifford et al. (2016) A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection. Cell Rep 16:1800-9
Jones, Hendrée E; Seashore, Carl; Johnson, Elisabeth et al. (2016) Measurement of neonatal abstinence syndrome: Evaluation of short forms. J Opioid Manag 12:19-23

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