S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: Outcome of a phase I study
- Kang, Won Ki; Park, Chaehwa; Yoon, Hyunah Lee; Kim, Won Seog; Yoon, Sung-Soo; Lee, Mark H.; Park, Keunchil; Kim, Kihyun; Jeong, Hyun Sik; Kim, Jeong-A; Nam, Seok-Jin; Yang, Jung-Hyun; Son, Young-Ik; Baek, Chung-Hwan; Han, Jungho; Ree, Howe J.; Lee, Eil Soo; Kim, Sun Hee; Kim, Dae-Won; Ahn, Yong Chan; Huh, Seung Jae; Choe, Yeon Hyeon; Lee, Je-Ho; Park, Mary H.; Kong, Gyoung-Sun; Park, Eun-Young; Kang, Yoon-Koo; Bang, Yung-Jue; Paik, Nam-Sun; Lee, Soon Nam; Kim, Seon-Hee; Kim, Sunyoung; Robbins, Paul D.; Tahara, Hideaki; Lotze, Michael T.; Park, Chan H.
- Issue Date
- Human Gene Therapy, Vol.12 No.6, pp.671-684
- 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 alpha (TNF-alpha) 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.
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