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Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: Outcome of a phase I study

Title
Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: Outcome of a phase I study
Authors
Won Ki KangPark C.Hyunah Lee YoonWon Seog KimYoon S.-S.Lee M.H.Park K.Kim K.Hyun Sik JeongKim J.-A.Nam S.-J.Yang J.-H.Son Y.-I.Baek C.-H.Han J.Ree H.J.Eil Soo LeeSun Hee KimKim D.-W.Yong Chan AhnSeung Jae HuhYeon Hyeon ChoeLee J.-H.Park M.H.Kong G.-S.Park E.-Y.Kang Y.-K.Bang Y.-J.Paik N.-S.Soon Nam LeeKim S.-H.Kim S.Robbins P.D.Tahara H.Lotze M.T.Park C.H.
Ewha Authors
이순남
SCOPUS Author ID
이순남scopus
Issue Date
2001
Journal Title
Human Gene Therapy
ISSN
1043-0342JCR Link
Citation
vol. 12, no. 6, pp. 671 - 684
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
A phase I dose-escalation clinical trial of peritumoral injections of interleukin 12 (IL-12)-transduced autologous fibroblasts was performed in patients with disseminated cancer for whom effective treatment does not exist. The goals of this study were to assess the safety and toxicities as well as the efficacy, and ancillarily the immunomodulatory effects, of peritumoral IL-12 gene transfer. Primary dermal fibroblasts cultured from the patients were transduced with retroviral vector carrying human IL-12 genes (p35 and p40) as well as the neomycin phosphotransferase gene (TFG-hIL-12-Neo). Patients received four injections at intervals of 7 days. Nine patients were enrolled in this dose-escalation study, with secreted IL-12 doses ranging from 300 ng/24 hr for the first three patients to 1000, 3000, and 5000 ng/24 hr for two patients in each subsequent dosage level. Although a definite statement cannot be made, there appears to be perturbation of systemic immunity. Also, the locoregional effects mediated by tumor necrosis factor α (TNF-α) and CD8+ T cells were observed with tumor regression. Treatment-related adverse events were limited to mild to moderate pain at the injection site; clinically significant toxicities were not encountered. Transient but clear reductions of tumor sizes were observed at the injected sites in four of nine cases, and at noninjected distant sites in one melanoma patient. Hemorrhagic necrosis of tumors was observed in two melanoma patients. These data indicate that gene therapy by peritumoral injection of IL-12-producing autologous fibroblasts is feasible, and promising in patients with advanced cancer.
DOI
10.1089/104303401300057388
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의학전문대학원 > 의학과 > Journal papers
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