title: Initial phase I safety of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 in degenerative arthritis patients.
abstract: BACKGROUND AIMS. TissueGene-C (TG-C) represents a cell-mediated gene therapy for localized delivery of allogeneic chondrocytes expressing transforming growth factor (TGF)-β1 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-β1-expressing chondrocytes (hChonJb#7) in order to help fill in the defect and as target cells for the actions of the expressed TGF-β1.
  
  
  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.
authors.affiliation: Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chul-Won
authors.initials: CW
authors.lastname: Ha
authors.forename: Moon Jong
authors.initials: MJ
authors.lastname: Noh
authors.forename: Kyoung Baek
authors.initials: KB
authors.lastname: Choi
authors.forename: Kwan Hee
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000368:Aged; D002356:Cartilage / Q000473:pathology; D019902:Chondrocytes / Q000166:cytology* / Q000637:transplantation*; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects*; D006801:Humans; D007270:Injections, Intra-Articular; D007718:Knee Injuries / Q000473:pathology / Q000628:therapy*; D007719:Knee Joint / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D012038:Regeneration; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1