ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 946

Phase 1 Study of Immunotherapy Using Autoantigen-Loaded Dendritic Cells in Patients with Anti-Citrullinated Peptide Antigen Positive Rheumatoid Arthritis

Young Bin Joo1, Jun-Eui Park2, Chan-Bum Choi3, Jeongim Choi1, Jin-ah Jang2, Minkyu Heo2, Hak-yeop Kim2, Hye-Soon Lee4, Yong-Soo Bae5 and Sang-Cheol Bae1, 1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 2JW CreaGene Research Institute, JWCreaGene Inc., Seongnam-si, South Korea, 3Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, South Korea, 41Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 53Department of Biological Science, Sungkyunkwan University, Suwon, South Korea

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy II: Novel Therapies in Rheumatoid Arthritis - Early in Development

Session Type: Abstract Submissions (ACR)

Background/Purpose

To date, no dendritic cell (DC) immunotherapy has been shown to give a benefit in patients with rheumatoid arthritis (RA). In this prospective phase I study, we evaluated the safety and clinical efficacy of autologous tolerogenic dendritic cell (DC) administration (CreaVax-RA) in patients with RA.

Methods

Twelve RA patients (six for low dose vaccination, 0.5 x 107 cells/injection and remaining six for high dose vaccination, 1.5 x 107 cells/injection) were administrated five times at 2 to 4 week intervals subcutaneously (around inguinal lymph nodes) with each CreaVax-RA, autologous semi-mature DCs pulsed with recombinant PAD4, RA33, citrullinated-filaggrin (cit-FLG) and vimentin antigens. Safety and clinical benefits together with associated immune responses were evaluated as primary and secondary outcomes, respectively, at 14 and 24 weeks after first administration. The major clinical outcomes were assessed by European League Against Rheumatism (EULAR) response.

Results

Among a total of 12 adverse events (AEs) in eight patients, 11 events (91.7%) were restricted in patients treated with low dose (0.5 x 107 cells/inj) while 1 event in patients with high dose (1.5 x 107 cells/inj). All of the AEs were grade 1 or 2 without over grade 3 AE. In ELISPOT assay, the number of IFN-γ-secreting T cells decreased in 91.7% (n = 11/12). The level of antigen-specific autoantibodies significantly decreased in 55.6% (n=5/9) among the autoantibody-positive patients against more than one autoantigen (p < 0.001). The percentage of patients who achieved a good-to-moderate EULAR response ranged over 58.3% (n = 7/12) at 14 weeks after initial administration. The response rate was much higher in high dose group than in low dose group (83.3% vs 33.3%, respectively). The patients without any autoantibodies showed no clinical efficacy

Conclusion

DC administration (CreaVax-RA) was safe and well tolerated in patients with RA in the present phase I study. Preliminary, but clinical outcomes were in good agreement with doses and immune responses. These phase I results warrant further clinical study of high dose CreaVax-RA (1.5 x 107/inj) in patients with RA.

Trial registration: CRiS KCT0000035

Clinical Research Information Service [Internet]; Osong (Chungchengbuk-do): Korea Centers for Disease Control and Prevention Ministry of Health and Welfare (Republic of Korea); 2010;KCT0000035; A phase I, open label, dose ranging study to evaluate the safety and tolerance of CreaVax-RA in active rheumatoid arthritis patients with usual DMARDs;

2010/09/14;[1 screen]. Available at:

http://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=1645 

Disclosure:

Y. B. Joo,
None;

J. E. Park,

JW CREAGENE,

3;

C. B. Choi,
None;

J. Choi,
None;

J. A. Jang,

JW CREAGENE,

3;

M. Heo,

JW CREAGENE,

3;

H. Y. Kim,

JW CREAGENE,

3;

H. S. Lee,
None;

Y. S. Bae,

JW CREAGENE,

1,

JW CREAGENE,

3;

S. C. Bae,
None.

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