Search

Antibody induction therapy is used in the majority of pediatric patients undergoing renal transplantation. Our center has previously reported short-term outcomes with TMG as induction therapy. We now present our experience over the last five yr. Patients received TMG intra- and post-operatively at a dose of 1.5 mg/kg/day. The dose was decreased to 0.75 mg/kg/day or held dependent on the patient's WBC and platelet counts. Post-transplant immunosuppression also included corticosteroids, MMF, and either TAC or CSA. Patient and graft survival, number of acute rejection episodes, creatinine clearance, incidence and type of infections, and trough levels of calcineurin inhibitor drugs were monitored during the follow-up period. Thirty-four renal transplants were performed in 33 pediatric patients ranging in age from 1.7 to 17.8 yr. Seventeen rejection episodes occurred during the time of follow-up with three patients having more than one episode, but only three episodes occurred within the first year after transplantation. Three patients had graft loss in the first week after transplantation from primary non-function (1) or technical failure/thrombosis (2). Graft losses occurred in seven additional patients during the time of follow-up with the first loss occurring at 17.7 months. Among patients with functional grafts at one wk after transplant, graft survival at one and three yr was 100% and 73% respectively. There were no patient deaths. There were no cases of post-transplant lymphoproliferative disease or other malignancy. One patient had symptomatic CMV disease. TMG is safe and effective as induction therapy in pediatric renal transplant patients. Late graft loss remains a challenge in the pediatric patient population, particularly in adolescents. [ABSTRACT FROM AUTHOR]

Background One of the major limitations to the use of adeno-associated virus (AAV) vectors for gene therapy has been the difficulty in producing enough vector to supply a clinical trial. More than 20 000 roller bottles may be required to generate AAV by the traditional transient transfection process to treat 50 patients. A scalable AAV producer cell line grown in serum-free media will meet the needs for the manufacture of AAV gene therapeutics. Methods A packaging cell line was generated by introducing the AAV rep and cap genes into A549 cells. From this packaging cell line, a number of producer cell lines were generated by infecting the packaging cell with the appropriate AAV vector. Producer cell lines were then adapted to serum-free suspension conditions for growth in bioreactors. Results We report here the development of six AAV producer cell lines that generate > 104 particles/cell. The rAAV vector preparations from these cell lines have physical and functional characteristics similar to rAAV vectors prepared by transient transfection. To enable large-scale production, producer cell lines were adapted to serum-free suspension and we demonstrate production of AAV at the 15 L scale. In addition, vector preparations from these cell lines were shown to be free of wild-type AAV. Conclusions AAV producer cell lines can be readily scaled to meet the needs of clinical trials. One 500 L bioreactor of these producer cells can produce the equivalent of 2500 high capacity roller bottles or 25 000 T-175 tissue culture flasks. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]