PMID- 12057850 OWN - NLM STAT- MEDLINE DCOM- 20030812 LR - 20190826 IS - 0165-2478 (Print) IS - 0165-2478 (Linking) VI - 83 IP - 1 DP - 2002 Aug 1 TI - Interleukin-12-gene transduction makes DCs from tumor-bearing mice an effective inducer of tumor-specific immunity in a peritoneal dissemination model. PG - 13-20 AB - Dendritic cells (DCs) from cancer patients, as well as tumor-infiltrating DCs, are reported to have suppressed immunostimulatory capacity. One of the major problems in the clinical use of DCs for treating tumors is that the DCs must be autologous ones obtained from patients. Compared with normal DCs (nDCs), flow-cytometric analysis and allogeneic mixed lymphocyte reaction (MLR) have revealed lower expression of the costimulatory molecules and suppressed T-cell-stimulatory activity in DCs derived from tumor-bearing mice (tDCs) despite of culture. We reported previously that the interleukin-12 (IL-12)-gene-transduced nDCs inhibited tumor growth due to induced tumor-specific Th1 and cytotoxic T cells (CTLs) in a murine established subcutaneous tumor model. In the present study, we examined whether tDCs could induce immune responses against tumors after IL-12-gene transduction in an established peritoneal dissemination model. The intraperitoneal injection of IL-12-gene-transduced tDCs resulted in prolonged survival of some treated mice (log-rank test; P=0.001) and tumor-specific Th1 and CTL activity. The injection of IL-12-gene-transduced nDCs prolonged the survival of all treated mice (P<0.0001) and elicited tumor-specific immunity, which were better than those of IL-12-gene-transduced tDCs. Taken together, DC modification of IL-12-gene transduction is an effective and promising approach for cancer therapy even when immunosuppressive tDCs are employed. FAU - Furumoto, Katsuyoshi AU - Furumoto K AD - Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan. furumoto@stanford.edu FAU - Mori, Akira AU - Mori A FAU - Yamasaki, Seiji AU - Yamasaki S FAU - Inoue, Naoya AU - Inoue N FAU - Yang, Weige AU - Yang W FAU - Nakau, Masayuki AU - Nakau M FAU - Yasuda, Seiichi AU - Yasuda S FAU - Arii, Shigeki AU - Arii S FAU - Imamura, Masayuki AU - Imamura M LA - eng PT - Journal Article PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 187348-17-0 (Interleukin-12) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adenocarcinoma/immunology/secondary/*therapy MH - Animals MH - Dendritic Cells/*immunology/transplantation MH - *Genetic Therapy MH - Interferon-gamma/metabolism MH - Interleukin-12/*genetics/immunology MH - Interleukin-4/metabolism MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Spleen/metabolism MH - *Transduction, Genetic MH - Tumor Cells, Cultured EDAT- 2002/06/12 10:00 MHDA- 2003/08/13 05:00 CRDT- 2002/06/12 10:00 PHST- 2002/06/12 10:00 [pubmed] PHST- 2003/08/13 05:00 [medline] PHST- 2002/06/12 10:00 [entrez] AID - S0165247802000718 [pii] AID - 10.1016/s0165-2478(02)00071-8 [doi] PST - ppublish SO - Immunol Lett. 2002 Aug 1;83(1):13-20. doi: 10.1016/s0165-2478(02)00071-8.