Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Safety and Biodistribution of An Adeno-Associated Virus Vector, AAV5 hIFN beta (ART-I02), Delivered Via Intra-Articular Injection to Rhesus Monkeys with Collagen-Induced Arthritis.

Aalbers1,  Caroline J., Bevaart1,  L., de Cortie1,  K., Vierboom2,  M.P.M., Wright3,  J.F., Tak4,  Paul P., Vervoordeldonk5,  Margriet

Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands
Biomedical Primate Research Centre, Rijswijk, Netherlands
Children's Hospital of Philadelphia, Philadelphia, PA
Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam The Netherlands, Amsterdam, Netherlands
Arthrogen B.V, Amsterdan, Netherlands


Recombinant AAV5.NFkB.hIFNb (ART-I02) is an adeno-associated type 5 (rAAV5) vector expressing the human interferon b (hIFNb) gene under control of an inflammation-inducible promoter, which is under development for the treatment of rheumatoid arthritis (RA). We investigated biodistribution and initial safety of the vector after intra-articular (ia) injection of the gene construct in rhesus monkeys with collagen-induced arthritis.


Mild arthritis was induced in 3 male and 3 female monkeys with chicken type II collagen (ChCII, 3 mg). All monkeys were naïve or showed limited (1:3.1–1:10) neutralizing antibody (Nab) titers to AAV5 at the start of the study. All animals were treated with a single dose of ART-I02 ia in the first involved PIP joint and in the ipsilateral knee and ankle joint (0.1, 0.5 and 1×10e13 vector genomes (vg), respectively). Clinical signs and symptoms were monitored for a maximum of 4 weeks until the human end-point in the study was reached. Serum, joints and organs were collected for histological analysis. Serum was analyzed for acute phase response (CRP, IL-6 levels) and Nab. Presence of ART-I02 vector genomes in 16 tissues was analyzed using qPCR. Expression of hIFNb was analyzed in serum and knee synovial tissue (ST) samples by ELISA. Histological evaluation by an experienced pathologist was performed on all organs collected to evaluate potential toxicity induced by the vector.


No adverse events were observed after ia injection of a high dose of ART-I02. All animals experienced a mild acute phase response (CRP > 50 mg/L-500 mg/L) with simultaneous rising of IL-6 levels and the production of anti-ChCII IgG antibodies, as expected in this model, associated with the development of mild arthritis. High titers of Nab to rAAV5 were observed (between 1:3.160 and 1:100.000) at the end of the study. Vector DNA was detected in ST of the injected knee joint and the popliteal (draining) lymph node (injected side) at the highest copy numbers. In 1 out of 3 animals one ovary tested positive for the vector DNA (100 copies/ug DNA). Importantly, no vector DNA was detected in testes (3/3) or brain (6/6). No abnormalities were observed after histological evaluation of all organs. In knee ST samples minimal expression of hIFNb was observed due to low arthritis activity in the knee joints, preventing activation of the NFkB promoter in the vector. In serum no hIFNb protein could be detected.


Intra-articular injection of a high dose of ART-I02 is well-tolerated and does not induce adverse events in the monkey collagen-induced arthritis model of RA. This study represents an important next step towards a phase I clinical trial in RA patients.

To cite this abstract, please use the following information:
Aalbers, Caroline J., Bevaart, L., de Cortie, K., Vierboom, M.P.M., Wright, J.F., Tak, Paul P., et al; Safety and Biodistribution of An Adeno-Associated Virus Vector, AAV5 hIFN beta (ART-I02), Delivered Via Intra-Articular Injection to Rhesus Monkeys with Collagen-Induced Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1147

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