title: Effective osteosarcoma cytolysis using cytokine-induced killer cells pre-inoculated with tumor RNA-pulsed dendritic cells.
abstract: Osteosarcoma with distant metastases at late stage has posed a challenge for novel therapeutic modalities. The application of cytokine-induced killer (CIK) cells to osteosarcoma constitutes a promising strategy. This approach had been studied in multiple myeloma and breast cancers, where CIK cells exhibited specific cytotoxicity toward malignant cells while sparing wild-type tissues. However, the consistency of CIK cell-induced anti-tumor cytotoxicity has not been thoroughly examined. We investigated whether autologous CIK cells could effectively induce cytolysis of cultured osteosarcoma cells. In addition to the observed CIK cell-induced osteosarcoma cytolysis, the pre-incubation of CIK cells with autologous dendritic cells pulsed with tumor's total RNA further enhanced the tumor cytolysis to greater than 6-fold. The anti-tumor cytolysis was optimized in complete autologous setting, and was attenuated with allogeneic components. The advantage of the co-culture with RNA-pulsed DC was lost when high CIK cell density was employed for anti-tumor cytotoxic assay, but was maintained in purified CD3(+)CD56(+) cells isolated from the CIK cells. This finding implied that CIK cells at limited cell density could induce effective osteosarcoma cytolysis with an aid from tumor antigen presentation on dendritic cell surface.
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand.
authors.forename: Adisak
authors.initials: A
authors.lastname: Wongkajornsilp
authors.forename: Sakdipat
authors.initials: S
authors.lastname: Sangsuriyong
authors.forename: Suradej
authors.initials: S
authors.lastname: Hongeng
authors.forename: Saranatra
authors.initials: S
authors.lastname: Waikakul
authors.forename: Apichat
authors.initials: A
authors.lastname: Asavamongkolkul
authors.forename: Sukit
authors.initials: S
authors.lastname: Huabprasert
mesh_terms: D001859:Bone Neoplasms / Q000473:pathology / Q000628:therapy*; D002452:Cell Count; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D012516:Osteosarcoma / Q000473:pathology / Q000628:therapy*; D012334:RNA, Neoplasm / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D012334:RNA, Neoplasm