Objective This study aimed to compare the anti-tumor effects of cytokine-induced killer (CIK) cellsinduced by autologous cytokines in patients with breast cancer and those of allogeneic CIK cells fromhealthy adults.Me...Objective This study aimed to compare the anti-tumor effects of cytokine-induced killer (CIK) cellsinduced by autologous cytokines in patients with breast cancer and those of allogeneic CIK cells fromhealthy adults.Methods We used conventional methods to induce CIK cells originating from two peripheral bloodmononuclear cell types (from patients with breast cancer and healthy adults). Killing activity was detectedusing an LDH assay, immunophenotypic changes were analyzed by flow cytometry, and the IFN-γ level ofculture supernatants was detected by ELISA.Results The results showed that the proliferative capacity of the allogeneic CIK cells was significantlyhigher than that of the autologous CIK cells. Compared with autologous CIK cells, the allogeneic CIK cellshad significantly enhanced anti-tumor activity against SKBR-3 cells (P < 0.01) and IFN-γ secretion (P <0.05);moreover, they increased the ratio of CD3+ CD56+ cells and CD3+ CD8+ cells (P < 0.05).Conclusion Healthy adult-derived induced CIK cells exhibited a stronger anti-tumor effect than inducedCIK cells derived from patients with breast cancer. The results of this study could provide experimentalevidence for the clinical application of CIK cells.展开更多
Objective： The aim of this study was to observe the therapeutic effect of cytokine induced killer （CIK） cells in combination with dendritic cells （DCs） on advanced solid carcinoma patients. Methods： Isolated per...Objective： The aim of this study was to observe the therapeutic effect of cytokine induced killer （CIK） cells in combination with dendritic cells （DCs） on advanced solid carcinoma patients. Methods： Isolated peripheral blood mononuclear cells （PBMCs） from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor （GM-CSF）, tumor necrosis factor-a （TNF-a） and interleukin-4 （IL-4） to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-y （IFN-y）, interleukin-2 （IL-2） and CD3 monoclonal antibody （CD3 McAb） to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients. Results： Forty-two patients with measurable nidus, 2 achieved complete remission （CR）, 9 partial remission （PR） and 15 stable disease （SD）, while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion： DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients.展开更多
Objective： To observe the effects of cytokine-induced killer （CIK） cells on the treatment of renal cell carcinoma. Methods： Twenty-eight postoperative cases with stage Ⅰ or stage Ⅱrenal cell carcinoma were admit...Objective： To observe the effects of cytokine-induced killer （CIK） cells on the treatment of renal cell carcinoma. Methods： Twenty-eight postoperative cases with stage Ⅰ or stage Ⅱrenal cell carcinoma were admitted in our hospital from January 2002 to June 2006, all cases were pathologically confirmed, and were divided into group A （18 cases） and group B （10 cases）. Group A was administrated 3-12 periods of CIK cells treatment combined with 5-7 cycles of IL-2 and INFα-2b, together with 4 cycles of chemotherapy （5-Fu ＋ CF）. Group B was given 4 cycles of chemotherapy （5-Fu ＋ CF） and 5-7 cycles of IL-2 and INFa-2b. Results： Three cases in group A had metastatic masses in two lungs within 1 year and died within 2 years postoperatively. The other 15 cases are still alive and in good health. Six cases in group B had metastatic masses in two lungs or/and in abdominal cavity within 1 year, and 4 of them died within 2 years. All the 6 cases died within 3 years. The other 4 cases are still alive and in good health. Conclusion： CIK cells are safe and effective for the treatment of stage I or stage II renal cell carcinoma, which should be further widely used.展开更多
Objective： To investigate the proliferation capabilities, immunophenotype changes, level of secreted cytokines and activities against lymphoma cells under the condition that cytokine-induced killer （CIK） cells co-c...Objective： To investigate the proliferation capabilities, immunophenotype changes, level of secreted cytokines and activities against lymphoma cells under the condition that cytokine-induced killer （CIK） cells co-cultured with dendritic cells （DC） in vitro. Methods： DC and CIK cells were induced from peripheral blood mononuclear cells of healthy volunteers. They were co-cultured meanwhile CIK cells were cultured alone as controls. Increased number of cells were counted by tapan-blue staining, killing activities were detected by MTT assay, immunophenotype changes were analyzed by flow cytometry, the IL-12 and INF-y levels of the cultured supernatants were detected by ELISA kits. Results： The proliferation capabilities of DC-CIK cells were significantly higher than that of CIK cells （P 〈 0.05）. Under the same condition, the ratio of double positive cells such as CD3^＋ CD8^＋, CD3^＋ CD56^＋ in CIK cells was significantly enhanced by co-cultured with DC cells （P 〈 0.05）. The level of IL-12 and INF-y secreted in supernatants was increased noticeably by co-cultured DC-CIK cells on day 3 compared to CIK cells which were cultured alone （P 〈 0.01 and P 〈 0.05）. Within the effector-target ratio range between 5：1 to 40：1, the activities against lymphoma cells of DC-CIK cells were much higher than that of CIK cells （P 〈 0.05）, and this effect was showed a positive correlation with the effector-target ratio. Conclusion： The proliferation capabilities, the level of secreted cytokines and the activities against lymphoma cells of DC-CIK cells were significantly higher than those of CIK cells. The research might provides theoretical and experimental basis for clinical immunotherapy of DC-CIK cells.展开更多
Objective: The aim of the study was to evaluate the effect of interleukin-12(IL-12) on the proliferation and cytotoxicity of cytokine-induced killer(CIK) cells in vitro. Methods: Three different combinations of cytoki...Objective: The aim of the study was to evaluate the effect of interleukin-12(IL-12) on the proliferation and cytotoxicity of cytokine-induced killer(CIK) cells in vitro. Methods: Three different combinations of cytokines, IL-2, IL-12 + IL-2, and IL-12, were used to proliferate CIK cells, adding IFN-γ, IL-1 and CD3 McAb in each one. Phenotype of the cells was analyzed by flow cytometry. The cellular proliferation and cytotoxic activity were determined by cytometry and MTT assay. Results: CIK cells generated by the three methods showed high reproductive activity, and no obviously difference in inducing CD3+CD56+ cells was found among the three groups. The group of IL-2 + IL-12 evidently enhanced both the proliferation and the cytotoxicity of the CIK cells compared with the other two groups(P < 0.05). Conclusion: IL-12 could be used to induce the CIK cells as well as IL-2. CIK cells induced by combining IL-12 with IL-2 had stronger proliferative ability and higher cytotoxicity to tumor cells in vitro, which could be used as a potential anti-tumor adoptive immunotherapy in clinic.展开更多
Objective： To study multi-directional derivation of cord blood mononuclear cells to CD3AK, LAK and CIK cells as well as changes of killing activity to gastric cancer cell strain in vitro. Methods： CD3mAb and IL-2 we...Objective： To study multi-directional derivation of cord blood mononuclear cells to CD3AK, LAK and CIK cells as well as changes of killing activity to gastric cancer cell strain in vitro. Methods： CD3mAb and IL-2 were used to induce CD3AK cells, and IL-2 was used to induce LAK cells; IFN-γ was used in the beginning, then IL-1, CD3mAb and IL-2 were used to induce CIK cells after 24 h for observing amplification and analyzing their relationship. The phenotypes of the cultured CIK cells were analyzed by flow cytometry. Subsequently, by using MGC-803 gastric cancer cell strain as target cells, the killing activity of CD3AK, LAK and CIK cells was evaluated by using MTT method. Results： The amplification activity of CD3AK and CIK cells was all far higher than LAK cells （P〈0.05）. The amplification activity had no obvious difference between CIK cells and CD3AK cells at prophase, but that was far higher in CIK cells than CD3AK cells at about 20^th day （P〈0.05）. The flow cytometry revealed that the amount of CD3^＋ CD56^＋ cells, major effector cells after CIK cells being cultured was significantly increased （P〈0.05）, moreover, the amount of CD8^＋ cells was significantly increased as well （P〈0.05）. The killing activities of CD3AK and CIK cells to the MGC-803 gastric cancer cell strain were all significantly higher than LAK cells, while the killing activity of CIK cells was stronger than CD3AK cells （P〈0.05）. Conclusion： CIK cells have stronger amplification activity and killing activity, and can be taken as more effective killing cells applied to the tumor adoptive immunotherapy.展开更多
基金Supported by a grant from the National Natural Sciences Foundation of Inner Mongolia(No.2012MS1102).
文摘Objective This study aimed to compare the anti-tumor effects of cytokine-induced killer (CIK) cellsinduced by autologous cytokines in patients with breast cancer and those of allogeneic CIK cells fromhealthy adults.Methods We used conventional methods to induce CIK cells originating from two peripheral bloodmononuclear cell types (from patients with breast cancer and healthy adults). Killing activity was detectedusing an LDH assay, immunophenotypic changes were analyzed by flow cytometry, and the IFN-γ level ofculture supernatants was detected by ELISA.Results The results showed that the proliferative capacity of the allogeneic CIK cells was significantlyhigher than that of the autologous CIK cells. Compared with autologous CIK cells, the allogeneic CIK cellshad significantly enhanced anti-tumor activity against SKBR-3 cells (P < 0.01) and IFN-γ secretion (P <0.05);moreover, they increased the ratio of CD3+ CD56+ cells and CD3+ CD8+ cells (P < 0.05).Conclusion Healthy adult-derived induced CIK cells exhibited a stronger anti-tumor effect than inducedCIK cells derived from patients with breast cancer. The results of this study could provide experimentalevidence for the clinical application of CIK cells.
基金Supported by a grant from the Foundation of Chongqing Municipal Health Bureau (No. 2010-2-301)
文摘Objective： The aim of this study was to observe the therapeutic effect of cytokine induced killer （CIK） cells in combination with dendritic cells （DCs） on advanced solid carcinoma patients. Methods： Isolated peripheral blood mononuclear cells （PBMCs） from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor （GM-CSF）, tumor necrosis factor-a （TNF-a） and interleukin-4 （IL-4） to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-y （IFN-y）, interleukin-2 （IL-2） and CD3 monoclonal antibody （CD3 McAb） to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients. Results： Forty-two patients with measurable nidus, 2 achieved complete remission （CR）, 9 partial remission （PR） and 15 stable disease （SD）, while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion： DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients.
文摘Objective： To observe the effects of cytokine-induced killer （CIK） cells on the treatment of renal cell carcinoma. Methods： Twenty-eight postoperative cases with stage Ⅰ or stage Ⅱrenal cell carcinoma were admitted in our hospital from January 2002 to June 2006, all cases were pathologically confirmed, and were divided into group A （18 cases） and group B （10 cases）. Group A was administrated 3-12 periods of CIK cells treatment combined with 5-7 cycles of IL-2 and INFα-2b, together with 4 cycles of chemotherapy （5-Fu ＋ CF）. Group B was given 4 cycles of chemotherapy （5-Fu ＋ CF） and 5-7 cycles of IL-2 and INFa-2b. Results： Three cases in group A had metastatic masses in two lungs within 1 year and died within 2 years postoperatively. The other 15 cases are still alive and in good health. Six cases in group B had metastatic masses in two lungs or/and in abdominal cavity within 1 year, and 4 of them died within 2 years. All the 6 cases died within 3 years. The other 4 cases are still alive and in good health. Conclusion： CIK cells are safe and effective for the treatment of stage I or stage II renal cell carcinoma, which should be further widely used.
基金the Shanxi Social Development Key Fundation (No. 2007k0902)
文摘Objective： To investigate the proliferation capabilities, immunophenotype changes, level of secreted cytokines and activities against lymphoma cells under the condition that cytokine-induced killer （CIK） cells co-cultured with dendritic cells （DC） in vitro. Methods： DC and CIK cells were induced from peripheral blood mononuclear cells of healthy volunteers. They were co-cultured meanwhile CIK cells were cultured alone as controls. Increased number of cells were counted by tapan-blue staining, killing activities were detected by MTT assay, immunophenotype changes were analyzed by flow cytometry, the IL-12 and INF-y levels of the cultured supernatants were detected by ELISA kits. Results： The proliferation capabilities of DC-CIK cells were significantly higher than that of CIK cells （P 〈 0.05）. Under the same condition, the ratio of double positive cells such as CD3^＋ CD8^＋, CD3^＋ CD56^＋ in CIK cells was significantly enhanced by co-cultured with DC cells （P 〈 0.05）. The level of IL-12 and INF-y secreted in supernatants was increased noticeably by co-cultured DC-CIK cells on day 3 compared to CIK cells which were cultured alone （P 〈 0.01 and P 〈 0.05）. Within the effector-target ratio range between 5：1 to 40：1, the activities against lymphoma cells of DC-CIK cells were much higher than that of CIK cells （P 〈 0.05）, and this effect was showed a positive correlation with the effector-target ratio. Conclusion： The proliferation capabilities, the level of secreted cytokines and the activities against lymphoma cells of DC-CIK cells were significantly higher than those of CIK cells. The research might provides theoretical and experimental basis for clinical immunotherapy of DC-CIK cells.
基金Supported by grants from the National Natural Science Foundation of China(No.39270765)Foundation of Heilongjiang (No.D201171)Heilongjiang Health Department(No.2006-478)
文摘Objective: The aim of the study was to evaluate the effect of interleukin-12(IL-12) on the proliferation and cytotoxicity of cytokine-induced killer(CIK) cells in vitro. Methods: Three different combinations of cytokines, IL-2, IL-12 + IL-2, and IL-12, were used to proliferate CIK cells, adding IFN-γ, IL-1 and CD3 McAb in each one. Phenotype of the cells was analyzed by flow cytometry. The cellular proliferation and cytotoxic activity were determined by cytometry and MTT assay. Results: CIK cells generated by the three methods showed high reproductive activity, and no obviously difference in inducing CD3+CD56+ cells was found among the three groups. The group of IL-2 + IL-12 evidently enhanced both the proliferation and the cytotoxicity of the CIK cells compared with the other two groups(P < 0.05). Conclusion: IL-12 could be used to induce the CIK cells as well as IL-2. CIK cells induced by combining IL-12 with IL-2 had stronger proliferative ability and higher cytotoxicity to tumor cells in vitro, which could be used as a potential anti-tumor adoptive immunotherapy in clinic.
文摘Objective： To study multi-directional derivation of cord blood mononuclear cells to CD3AK, LAK and CIK cells as well as changes of killing activity to gastric cancer cell strain in vitro. Methods： CD3mAb and IL-2 were used to induce CD3AK cells, and IL-2 was used to induce LAK cells; IFN-γ was used in the beginning, then IL-1, CD3mAb and IL-2 were used to induce CIK cells after 24 h for observing amplification and analyzing their relationship. The phenotypes of the cultured CIK cells were analyzed by flow cytometry. Subsequently, by using MGC-803 gastric cancer cell strain as target cells, the killing activity of CD3AK, LAK and CIK cells was evaluated by using MTT method. Results： The amplification activity of CD3AK and CIK cells was all far higher than LAK cells （P〈0.05）. The amplification activity had no obvious difference between CIK cells and CD3AK cells at prophase, but that was far higher in CIK cells than CD3AK cells at about 20^th day （P〈0.05）. The flow cytometry revealed that the amount of CD3^＋ CD56^＋ cells, major effector cells after CIK cells being cultured was significantly increased （P〈0.05）, moreover, the amount of CD8^＋ cells was significantly increased as well （P〈0.05）. The killing activities of CD3AK and CIK cells to the MGC-803 gastric cancer cell strain were all significantly higher than LAK cells, while the killing activity of CIK cells was stronger than CD3AK cells （P〈0.05）. Conclusion： CIK cells have stronger amplification activity and killing activity, and can be taken as more effective killing cells applied to the tumor adoptive immunotherapy.
