Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Dendritic Cell-Based Immunotherapy Combined with Low-Dose Methothrexate Is Effective in the Treatment of Advanced Collagen-Induced Arthritis in Mice.
Kang4, Mi-Sun, Lee4, Jung-Wook, Lee4, Hyun-Soo, Choi1, Chan-Bum, Lee3, Hye-Soon, Bae2, Sang-Cheol, Bae5, Yong-Soo
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of Korea
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases
Research Institute for DC Immunotherapy, CreaGene Inc.
Research Institute for DC Immunotherapy, CreaGene Inc., Department of Biological Science Sungkyunkwan University
We have previously demonstrated that semi-mature dendritic cells (smDC)-based immunotherapy was effective in the treatment of early stage collagen-induced arthritis (CIA). This work was initiated to determine the efficacy of combination therapy with smDC and methotrexate (MTX) in advanced stage of CIA mice.
CIA mice in arthritis score 23 (56 weeks after primary CII inoculation) were treated with MTX and collagen-loaded smDCs (CII-smDC) in three consecutive therapeutic cycles. Each therapeutic cycle was completed by administration of MTX three times on days 2, 4 and 6, followed by administration of CII-smDC on day 7. Footpad thickness and the disease severity of each mouse were measured once or twice a week for 90 days after completion of three therapeutic cycles. Foxp3-positive regulatory T cell (Treg) populations, Th1/Th2 immune response, and cytokine profiles were assessed in the spleen and lymph nodes.
Combination therapy with low-dose (0.5mg/kg) MTX and CII-smDC was more effective than high or low dose MTX alone or combination of high dose MTX and CII-smDC in inhibiting disease progression. Treatment with CII-smDC alone also showed comparable effect. CD4+Foxp3+ Treg populations were markedly increased in mice treated with the combination therapy compared to mice treated with CII-smDC alone as well as other treatments. IL-10 secretion also increased in proportion to the level of induced Treg. The combination therapy reduced the secretion of interferon gamma (IFN-g), but did not affect or slightly increased the IL-4 secretion in the mixed lymphocyte reaction with spleen or lymph node T cells. Treg induced by combination therapy were effective in inhibiting CII-specific T cell proliferation. However, total CD4+ T cell populations were not significantly changed by the combination therapy.
Combination therapy with low-dose MTX and smDC, or smDC alone, was efficacious in the treatment of advanced arthritis mice by inducing antigen-specific Treg population, rather than changing Th1/Th2 immune deviation, followed by blocking autoreactive T cell proliferation, resulting in disease control.
To cite this abstract, please use the following information:
Kang, Mi-Sun, Lee, Jung-Wook, Lee, Hyun-Soo, Choi, Chan-Bum, Lee, Hye-Soon, Bae, Sang-Cheol, et al; Dendritic Cell-Based Immunotherapy Combined with Low-Dose Methothrexate Is Effective in the Treatment of Advanced Collagen-Induced Arthritis in Mice. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1714