TG‑C is a cell-mediated gene therapy for the treatment of knee osteoarthritis (OA). In this preclinical study we employed rats and goats to demonstrate the pre-clinical safety of TG-C.
All animal studies were conducted with ethical committee permission and approval and in line with the World Medical Association (WMA) Declaration of Helsinki and NC3Rs ARRIVE guidelines to ensure the welfare of animals used for research. 2x106 / ml (20 μl) TG-C cells (48Gy-irradiated) were injected into the knee joints of 70 (35 male and 35 female) Sprague-Dawley (SD) rats. Quantitative PCR (qPCR) was used to detect human cells and RvTGFβ1 vector-transduced cells. Safety studies in goats examined a total of 71 animals. Goats received high and low doses of TG-C; 10 animals received a high single-dose of 5x107 cells/ml (500 μl); 10 animals received a low dose single-dose of 1x107 cells/ml (500 μl); 10 animals received a high multiple-dose 5x107 cells/ml (500 μl) and were followed up for 6 and 12 months.
Real-time qPCR was performed to determine if human TG-C cells can be detected the knee joints and other organs. Treatment with TG-C had no effect on mortality, body weight, or gross or microscopic pathology of the injection site in rats. Safety studies in goats revealed no adverse findings, either systemically or locally at the 6 or 12-month timepoints. TG-C was well tolerated and did not elicit any immune responses in the goats either in the low, high, single or multiple doses.
The radiation inactivation of cell proliferation in the GP2-293 component of TG C underlines the suitability for intra-articular injection into the knee joint. The introduction of a gamma or x-ray radiation inactivation step in the preclinical development pipeline for TG-C highlights the utility of this approach for developing other cell-based approaches for the intra-articular treatment of OA.