Coculturing Dendritic Cells with Zoledronate Acid Efficiently Enhance the Anti-Tumor Effects of Cytokine-Induced Killer Cells.

Xiaosan Su; Lei Zhang; Liangkun Jin; Junsong Ye; Zheng Guan; Rui Chen

Introduction: Dendritic cells (DCs) have greater stimulating activity on innate and adaptive immunity following short-term sensitization with zoledronate acid (DCs). We identified the phenotype, cytotoxicity, and mechanisms of killing of cytokine-induced killer (CIK) cells which were cocultured with DCs. Methods: Adherent and nonadherent cells of peripheral blood mononuclear cell from myeloma patients were incubated for DCs and CIK cells. Then, the CIK cells were cocultured with DCs (DCs-CIK). Expression of markers for DCs-CIK cells was measured using flow cytometry. Cytotoxicity was evaluated by against human myeloma cell lines and mechanisms of killing were tested by selectively blocking NKG2D receptor. The anti-tumor activity of these effector cells was further evaluated using a nude mice tumor model. Results: γδ TCR expression of CIK cells significantly increased after coculture with immature or mature DCs (iDCs/mDCs-CIK) and these cells aggressively lysed myeloma cells compared with mDCs-CIK and zoledronate acid pulsed CIK cells (CIK; 50.8 ± 7.9% and 48.2 ± 4.7% versus 31.9 ± 5.1% and 20.5 ± 3.6%, effector versus target ratio was 60:1). Both αβ T and γδ T cells in the iDCs-CIK cells performed the majority of lysis. The iDCs/mDCs-CIK cells greatly increased NKG2D expression compared with mDCs-CIK and CIK during culture (71.5 ± 11.3% and 67.7 ± 9.3% versus 51.3 ± 6.2% and 47.1 ± 5.7%). iDCs-CIK cell-mediated lysis dropped 69.21% when the NKG2D receptor was blocked and the cytotoxicity correlated with NKG2D ligand–MICA expression on the target cells. In a human myeloma bearing nude mice model, iDCs-CIK and mDCs-CIK cells treatment groups obtained 75% and 62.5% long-term survival (>120 days) respectively, as compared with none of the control animals or 37.5% treated with mDCs-CIK cells. Conclusion: Large numbers of CIK cells with greater anti-tumor activities are rapidly generated by Zol-treated iDCs/mDCs. This strategy is worthy of further investigation to improve adoptive cell therapy against tumors.

DENDRITIC cells; TUMOR prevention; KILLER cells; CELLULAR mechanics; IMMUNE system; CLINICAL immunology

Journal of Clinical Immunology, 2010, Vol 30, Issue 5, p766

0271-9142

Academic Journal

10.1007/s10875-010-9434-1