Initial phase I safety of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 in degenerative arthritis patients

被引:117
作者
Ha, Chul-Won [1 ]
Noh, Moon Jong [2 ]
Choi, Kyoung Baek [3 ]
Lee, Kwan Hee [2 ,4 ]
机构
[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Orthoped Surg, Seoul, South Korea
[2] TissueGene Inc, Rockville, MD USA
[3] Kolon Life Sci Inc, Inchon, South Korea
[4] Inha Univ, Coll Med, Clin Res Ctr, Inchon, South Korea
关键词
cell-mediated therapy; degenerative arthritis; phase I clinical study; transforming growth factor-beta-1; GROWTH-FACTOR-BETA; BONE MORPHOGENETIC PROTEIN-2; ARTICULAR-CARTILAGE; PROTEOGLYCAN SYNTHESIS; OSTEOGENIC PROTEIN-1; HYALINE CARTILAGE; TGF-BETA; REPAIR; KNEE; DEFECTS;
D O I
10.3109/14653249.2011.629645
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background aims. TissueGene-C (TG-C) represents a cell-mediated gene therapy for localized delivery of allogeneic chondrocytes expressing transforming growth factor (TGF)-beta 1 directly to the damaged knee joint. Untransduced human chondrocytes (hChonJ cells) have also been incorporated into the TG-C product at a 3:1 ratio with TGF-beta 1-expressing chondrocytes (hChonJb##7) in order to help fill in the defect and as target cells for the actions of the expressed TGF-beta 1. Methods. A phase I dose-escalating clinical trial was performed to evaluate the safety and biologic activity of TG-C in patients with advanced osteoarthritis of the knee joint (full thickness cartilage defect) that was refractory to existing non-operative therapies. Following a single intra-articular injection into the joint space of the damaged knee, patients were monitored for safety, and an evaluation was performed to assess the pharmacokinetics and biologic activity of TG-C. Results. There were no treatment-related serious adverse events. Swelling, effusion and minor localized reactions such as warming sensation or itching were observed in a dose-dependent manner at the injection site. Knee evaluation scores seemed to indicate a dose-dependent trend toward efficacy; however, patient numbers were not sufficient to determine statistical significance. Conclusions. Overall, there were no significant safety issues related to the administration of TG-C, with only some minor injection site reactions observed. Additionally, knee scoring analyzes indicated a possibility that TG-C may contribute to improvement of arthritic symptoms. More study is warranted to evaluate further the safety and determine the potential efficacy of TG-C.
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页码:247 / 256
页数:10
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