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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Effective osteosarcoma cytolysis using cytokine-induced killer cells pre-inoculated with tumor RNA-pulsed dendritic
Adisak Wongkajornsilp1, Sakdipat Sangsuriyong, Suradej Hongeng
1Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand.
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.
Insights
Cytokine-induced killer (CIK) cells show promise for treating osteosarcoma. Combining CIK cells with dendritic cells pulsed with tumor RNA significantly enhanced their ability to destroy cancer cells.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Osteosarcoma with distant metastases presents a significant therapeutic challenge.
- Cytokine-induced killer (CIK) cells have shown efficacy against various cancers, including multiple myeloma and breast cancer.
- The effectiveness of CIK cells against osteosarcoma requires further investigation.
Purpose of the Study:
- To evaluate the efficacy of autologous CIK cells in inducing cytolysis of cultured osteosarcoma cells.
- To determine if combining CIK cells with dendritic cells (DCs) pulsed with tumor RNA enhances anti-tumor activity.
- To investigate the optimal conditions for CIK cell-mediated osteosarcoma treatment.
Main Methods:
- Cultured osteosarcoma cells were treated with autologous CIK cells.
- CIK cells were co-cultured with autologous dendritic cells pulsed with tumor RNA.
- Cytotoxicity assays were performed using varying CIK cell densities and components (autologous vs. allogeneic).
- Purified CD3(+)CD56(+) cells from CIK cultures were analyzed.
Main Results:
- Autologous CIK cells demonstrated cytolysis of osteosarcoma cells.
- Pre-incubation with RNA-pulsed autologous dendritic cells enhanced osteosarcoma cytolysis over six-fold.
- Optimal anti-tumor activity was achieved with a complete autologous system.
- The enhancement from RNA-pulsed DCs was diminished at high CIK cell densities but maintained in purified CD3(+)CD56(+) cells.
Conclusions:
- Autologous CIK cells can effectively induce osteosarcoma cell cytolysis.
- Co-culture with RNA-pulsed dendritic cells significantly potentiates CIK cell anti-tumor activity.
- Effective osteosarcoma lysis by CIK cells at limited densities is aided by tumor antigen presentation on dendritic cells.
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