Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients
- PMID: 26041704
- DOI: 10.1126/scitranslmed.aaa9301
Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients
Abstract
In animals, immunomodulatory dendritic cells (DCs) exposed to autoantigen can suppress experimental arthritis in an antigen-specific manner. In rheumatoid arthritis (RA), disease-specific anti-citrullinated peptide autoantibodies (ACPA or anti-CCP) are found in the serum of about 70% of RA patients and are strongly associated with HLA-DRB1 risk alleles. This study aimed to explore the safety and biological and clinical effects of autologous DCs modified with a nuclear factor κB (NF-κB) inhibitor exposed to four citrullinated peptide antigens, designated "Rheumavax," in a single-center, open-labeled, first-in-human phase 1 trial. Rheumavax was administered once intradermally at two progressive dose levels to 18 human leukocyte antigen (HLA) risk genotype-positive RA patients with citrullinated peptide-specific autoimmunity. Sixteen RA patients served as controls. Rheumavax was well tolerated: adverse events were grade 1 (of 4) severity. At 1 month after treatment, we observed a reduction in effector T cells and an increased ratio of regulatory to effector T cells; a reduction in serum interleukin-15 (IL-15), IL-29, CX3CL1, and CXCL11; and reduced T cell IL-6 responses to vimentin(447-455)-Cit450 relative to controls. Rheumavax did not induce disease flares in patients recruited with minimal disease activity, and DAS28 decreased within 1 month in Rheumavax-treated patients with active disease VSports手机版. This exploratory study demonstrates safety and biological activity of a single intradermal injection of autologous modified DCs exposed to citrullinated peptides, and provides rationale for further studies to assess clinical efficacy and antigen-specific effects of autoantigen immunomodulatory therapy in RA. .
Copyright © 2015, American Association for the Advancement of Science. V体育安卓版.
Comment in
-
Rheumatoid arthritis: First-in-human phase I trial of DC immunotherapy for early RA.Nat Rev Rheumatol. 2015 Aug;11(8):443. doi: 10.1038/nrrheum.2015.90. Epub 2015 Jun 23. Nat Rev Rheumatol. 2015. PMID: 26100972 No abstract available.
Publication types
- VSports注册入口 - Actions
MeSH terms
- "V体育2025版" Actions
- Actions (VSports app下载)
- VSports - Actions
- "V体育安卓版" Actions
Substances
- "VSports最新版本" Actions
- Actions (V体育官网)
- Actions (VSports注册入口)
"VSports app下载" Associated data
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous (V体育平台登录)