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Kunming, China

Su X.,Biomedical Research Center | Zhang L.,Biomedical Research Center | Jin L.,First Hospital of Kunming | Ye J.,Biomedical Research Center | And 2 more authors.
Journal of Clinical Immunology | Year: 2010

Introduction: Dendritic cells (DCs) have greater stimulating activity on innate and adaptive immunity following short-term sensitization with zoledronate acid (DCsZol). We identified the phenotype, cytotoxicity, and mechanisms of killing of cytokine-induced killer (CIK) cells which were cocultured with DCsZol. 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 DCsZol (DCsZol-CIK). Expression of markers for DCsZol-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 DCsZol (iDCs/mDCsZol-CIK) and these cells aggressively lysed myeloma cells compared with mDCs-CIK and zoledronate acid pulsed CIK cells (CIKZol; 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 iDCsZol-CIK cells performed the majority of lysis. The iDCs/mDCsZol-CIK cells greatly increased NKG2D expression compared with mDCs-CIK and CIKZol during culture (71.5 ± 11.3% and 67.7 ± 9.3% versus 51.3 ± 6.2% and 47.1 ± 5.7%). iDCsZol-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, iDCsZol-CIK and mDCsZol-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. © 2010 Springer Science+Business Media, LLC.

Chen X.,Kunming Medical University | Liu Z.,Kunming Medical University | Huang Y.,Kunming Medical University | Li R.,Kunming Medical University | And 8 more authors.
Autoimmunity | Year: 2014

Background: The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research into their potential use in immunotherapy in the treatment of cancer. In this study, we examined the efficacy of dendritic cell-tumor cell fusion hybrid vaccines in eliciting an immune response against Lewis lung carcinoma (LLC) cells, as compared to other types of tumor vaccines. In addition, we also tested whether the efficacy of the vaccines was affected by the route of administration. Four different tumor vaccines were compared: (1) HC (hybrid cell), consisting of DC/LLC hybrids; (2) DC+LLC (DCs pulsed with apoptotic LLCs); (3) DC without antigen loading/pulsing; (4) LLC (apoptotic/irradiated tumor cells). We also compared four different routes of administration for each vaccine: (1) Preimmunization; (2) Vaccination therapy; (3) Adoptive immunotherapy; (4) Vaccination therapy combined with adoptive immunotherapy. Anti-tumor immunity was assessed in vivo and the CTL (cytotoxic T lymphocyte) response as well as the expression of key cytokines, IFN-γ and IL-10 were further evaluated using in vitro assays. Results: Our data demonstrate that vaccination with HC hybrids provides more effective anti-tumor protective immunity and significantly greater therapeutic immunity than vaccination with DC+LLC, DC or LLC. Most remarkably, vaccination therapy with HC hybrids was more successful than combination (vaccination+adoptive) therapy for the induction of anti-tumor responses. Splenocytes harvested from mice immunized with HC hybrids demonstrated the greatest cytotoxic T lymphocyte (CTL) activity and their production of IFN-γ was high, while their production of IL-10 was very low. Conclusions: Our results suggest that vaccination therapy with DC-tumor cell fusion hybrids provides more effective protection against lung cancer. © 2014 Informa UK Ltd.

Su X.,Biomedical Research Center | Zhang L.,Biomedical Research Center | Jin L.,First Hospital of Kunming | Ye J.,Biomedical Research Center | And 3 more authors.
Cancer Biotherapy and Radiopharmaceuticals | Year: 2010

Cytokine-induced killer (CIK) cells have shown antitumor activity against several tumor cells both in vitro and in vivo. This study reports on the large-scale expansion of CIK cells and also present preliminary results from a pilot clinical trial. Sixteen (16) patients with renal cell carcinoma (RCC), all of whom had metastases after radical nephrectomy and adjuvant therapy using interferon-α (IFN-α) and/or interleukin-2 (IL-2), were treated with CIK cells. CIK cells were generated from peripheral blood mononuclear cells (PBMCs) and incubated in the presence of IFN-γ followed by OKT3 and IL-2. Treatment schedule consisted of two to three cycles of CIK cell infusions at an interval of 3 weeks. A total of 46 infusions were administered to 16 metastatic RCC (mRCC) patients. The median number of transferred cells per treatment was 6.7 × 109 (range, 2.5-12.3). At a 60:1 effector-target cell ratio, CIK cells killed 51.4% and 32.1% of two human kidney tumor cell lines (293 and SK-RC-42), respectively. After CIK cell infusion, the percentage of CD3+, CD8+, CD3+CD56+, and NKG2D+ cells and the intracellular products of two type 1 cytokines (IFN-γ and tumor necrosis factor α) significantly increased in the patients' PBMCs. Toxicity was minimal, and there were no immediate adverse reactions to the infusions. Three (3) patients had complete response, 1 patient had partial response, and 6 patients had stable disease. These results showed that adoptive CIK cell immunotherapy is a safe and effective treatment, which may have essential benefits for the improvement of the immunologic function in mRCC patients and play an important role in the treatment of mRCC. © 2010, Mary Ann Liebert, Inc.

Hu J.,Central South University | Lv G.,Central South University | Zhou S.,Central South University | Zhou S.,Hunan University | And 5 more authors.
PLoS ONE | Year: 2015

Background: Osteosarcoma is the most common primary bone malignancy in children and young adults. Increasing results suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for osteosarcoma. Methods: MiR-182 expression level in osteosarcoma cell lines and tissues were assayed by qRT-PCR. MiRNA mimics or inhibitor were transfected for up-regulation or down-regulation of miR-182 expression. Cell function was assayed by CCK8, migration assay and invasion assay. The target genes of miR-182 were predicated by bioinformatics algorithm (TargetScan Human). Results: MiR-182 was down-regulated in osteosarcoma tissues and cell lines. Overexpression of miR-182 inhibited tumor growth, migration and invasion. Subsequent investigation revealed that TIAM1 was a direct and functional target of miR-182 in osteosarcoma cells. Overexpression of miR-182 impaired TIAM1-induced inhibition of proliferation and invasion in osteosarcoma cells. Conclusions: Down-expression of miR-182 in osteosarcoma promoted tumor growth, migration and invasion by targeting TIAM1. MiR-182 might act as a tumor suppressor gene whose downregulation contributes to the progression and metastasis of osteosarcoma, providing a potential therapy target for osteosarcoma patients. © 2015 Hu et al.

Su X.,Biomedical Research Center | Zhang L.,Biomedical Research Center | Wu S.,First Hospital of Kunming | Jin L.,First Hospital of Kunming | And 3 more authors.
Cancer Biotherapy and Radiopharmaceuticals | Year: 2011

Adoptive tumor-infiltrating lymphocytes (TILs) therapy has demonstrated drastic effects on advanced malignant melanoma. Intensive pretreatment such as chemotherapy and/or total body irradiation has been used to eliminate immunosuppressive components and therefore enhances the antitumor effects of TILs. However, these pretreatments may cause severe side effects, especially for elderly patients. This case observes the complete response of how a patient with metastatic melanoma was treated sequentially with local tumor resection, postoperative adoptive cytokine-induced killer cells and TILs infusion. In addition, the cascading adoptive cell therapy was well-tolerated by the patient. Therefore, being pretreated with cytokine-induced killer cells could ameliorate the immunosuppressive condition in the patient and provide a favorable circumstance for subsequent TILs infusion. The further adoptive TILs therapy could exert the most powerful antitumor activity in such an amicable circumstance. © 2011, Mary Ann Liebert, Inc.

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