Malignant gliomas are the most devastating tumors in clinical practice and nave poorest survival, Immunological treatment of such patients may likely increase the survival and quality of life. Dendritic cells （DCs）,...Malignant gliomas are the most devastating tumors in clinical practice and nave poorest survival, Immunological treatment of such patients may likely increase the survival and quality of life. Dendritic cells （DCs）, most potent antigen presenting cells in combination with oral chemotherapeutic agents may be tried for patients giving consent to such treatment. We have successfully combined the two therapies in an adult male patient who was on downhill course after being operated on once with post operation chemotherapy and radiotherapy for glioma in the left parietal area. He received five dendritic cell therapy vaccines in combination with oral chemotherapy and responded dramatically having near normal quality of life for an additional five months with this regime, increasing the survival after operation to 11 months. This therapy is continuing with radiological betterment of the lesion. The DCs are matured with antigen extracted from wax embedded tissue at 6th day of culture. We feel that the treatment can be given to more number of patients to establish its efficacy for the dreaded cancer glioblastoma multiforme.展开更多
Objective： To investigate the antitumor activity of tumor lysate-pulsed dendritic cells vaccine in RM-1 prostate cancer mice model with the survival time of mice calculated and the tumor size measured in DC vaccine t...Objective： To investigate the antitumor activity of tumor lysate-pulsed dendritic cells vaccine in RM-1 prostate cancer mice model with the survival time of mice calculated and the tumor size measured in DC vaccine therapy. Methods： C57BL/6 mice were immunized on the dorsal flank by s.c. inoculation of Lysate-DC, ova-DC, and non-DC on day -7. On day 0, 2× 10^6cells of RM-1 tumor cells （H-2b） were injected s.c. in C57BL/6 mice pre-treated by s.c. inoculation of modified DCs, correspondingly. DTH assay was performed with modified DCs. In partial test, for the determination of which immune cells were required for antitumor activity, mice were immunodepleted of CD4, CDS, or natural killer （NK） NK1.1 cells with the corresponding monoclonal antibodies. The survival time of nude mice loaded with tumor cells was calculated and the size of tumor measured. Results： In RM-1 mice prostate cancer model, immunized with lysate-DC, compared with ova-DC and non-DC, the pre-infection vaccine resulted in 100% clearance of primary tumors, whereas on day 0 of injection vaccine cleared 40-60% of primary tumors. On day 0, C57BL/6 mice （H-2b） were immunized with Lysate-DC, compared with ova-DC and non-DC by caudal vein injection, then on day 15, RM-1 cells were inoculated. On day 30, average diameters of tumor in different groups of modified DC were 23.7±5.4 mm, 22.1±4.9 mm, 4.3±2.6 mm, respectively. Lysate-DC, compared with ova-DC and non-DC, can greatly depressed RM-1 tumor cell growth （P〈0.01）. The mean survival time of C57BL/6 mice in Lysate-DC, ova-DC and non-DC groups were 15.8±2.6, 16.6±3.2, 39.0±5.6, respectively, and there was a significant difference in the mean survival time in lysate-DC group between ova-DC and non-DC group （P〈0.01）. DTH test showed that lysate-DC could prime T lymphocyte and elicit tumor antigen specific immune response, and over 80% mice in groups of lysate-DC showed obvious swelling in their foot pad. This response was strengthened with repeating inoculation, whereas DTH response was not seen in control group. In vivo depletion of NK cells resulted in a 40-60% reduction in growth suppression within the primary tumor, and depletion of CD4^＋ cells resulted in a 20% reduction in growth suppression. Conclusion： The minor lysate-pulsed dendritic cells vaccine could elicit antitumor activity in RM-1 loaded C57BL/6 mice, and prolong the duration of RM-1 loaded C57BL/6 mice. So DC-based immunotherapy with hormone-refractory prostate carcinoma yielded protective immunity, generated efficient cellular antitumor responses, thereby providing further preclinical support for feasible immunotherapy approaches for prostate cancer.展开更多
Objective： Professional antigen-presenting dendritic cells （DCs） and cytokine-induced killer （CIK） cells, components of anti-cancer therapy, have shown clinical benefits and potential to overcome chemotherapeutic...Objective： Professional antigen-presenting dendritic cells （DCs） and cytokine-induced killer （CIK） cells, components of anti-cancer therapy, have shown clinical benefits and potential to overcome chemotherapeutic re- sistance. To evaluate whether DC-CIK cell-based therapy improves the clinical efficacy of chemotherapy, we reviewed the literature on DC-CIK cells and meta-analyzed randomized controlled trials （RCTs）. Methods： We searched several databases and selected studies using predeflned criteria. RCTs that applied chemotherapy with and without DC-CIK cells separately in two groups were included. Odds ratio （OR） and mean difference （MD） were reported to measure the pooled effect. Results： Twelve reported RCTs （826 patients）, which were all performed on Chinese patients, were included. Combination therapy exhibited better data than chemotherapy： 1-year overall survival （OS） （OR=0.22, P〈0.01）, 2-year OS （OR=0.28, P〈0.01）, 3-year OS （OR=0.41, P〈0.01）, 1-year disease-free survival （DFS） （OR=0.16, P〈0.05）, 3-year DFS （OR=0.32, P〈0.01）, objective response rate （ORR） （OR=0.54, P〈0.01）, and disease control rate （DCR） （OR=0.46, P〈0.01）. Moreover, the levels of CD3＋ T-lymphocytes （MD=-11.65, P〈0.05） and CD4＋ T-lymphocytes （MD=-8.18, P〈0.01） of the combination group were higher. Conclusions： Immunotherapy of DC-CIK cells may enhance the efficacy of chemotherapy on solid cancer and induces no specific side effect. Further RCTs with no publishing bias should be designed to confirm the immunotherapeutic effects of DC-CIK cells.展开更多
文摘Malignant gliomas are the most devastating tumors in clinical practice and nave poorest survival, Immunological treatment of such patients may likely increase the survival and quality of life. Dendritic cells （DCs）, most potent antigen presenting cells in combination with oral chemotherapeutic agents may be tried for patients giving consent to such treatment. We have successfully combined the two therapies in an adult male patient who was on downhill course after being operated on once with post operation chemotherapy and radiotherapy for glioma in the left parietal area. He received five dendritic cell therapy vaccines in combination with oral chemotherapy and responded dramatically having near normal quality of life for an additional five months with this regime, increasing the survival after operation to 11 months. This therapy is continuing with radiological betterment of the lesion. The DCs are matured with antigen extracted from wax embedded tissue at 6th day of culture. We feel that the treatment can be given to more number of patients to establish its efficacy for the dreaded cancer glioblastoma multiforme.
基金Supported by medical funds of Shanghai Science and Technology Commission
文摘Objective： To investigate the antitumor activity of tumor lysate-pulsed dendritic cells vaccine in RM-1 prostate cancer mice model with the survival time of mice calculated and the tumor size measured in DC vaccine therapy. Methods： C57BL/6 mice were immunized on the dorsal flank by s.c. inoculation of Lysate-DC, ova-DC, and non-DC on day -7. On day 0, 2× 10^6cells of RM-1 tumor cells （H-2b） were injected s.c. in C57BL/6 mice pre-treated by s.c. inoculation of modified DCs, correspondingly. DTH assay was performed with modified DCs. In partial test, for the determination of which immune cells were required for antitumor activity, mice were immunodepleted of CD4, CDS, or natural killer （NK） NK1.1 cells with the corresponding monoclonal antibodies. The survival time of nude mice loaded with tumor cells was calculated and the size of tumor measured. Results： In RM-1 mice prostate cancer model, immunized with lysate-DC, compared with ova-DC and non-DC, the pre-infection vaccine resulted in 100% clearance of primary tumors, whereas on day 0 of injection vaccine cleared 40-60% of primary tumors. On day 0, C57BL/6 mice （H-2b） were immunized with Lysate-DC, compared with ova-DC and non-DC by caudal vein injection, then on day 15, RM-1 cells were inoculated. On day 30, average diameters of tumor in different groups of modified DC were 23.7±5.4 mm, 22.1±4.9 mm, 4.3±2.6 mm, respectively. Lysate-DC, compared with ova-DC and non-DC, can greatly depressed RM-1 tumor cell growth （P〈0.01）. The mean survival time of C57BL/6 mice in Lysate-DC, ova-DC and non-DC groups were 15.8±2.6, 16.6±3.2, 39.0±5.6, respectively, and there was a significant difference in the mean survival time in lysate-DC group between ova-DC and non-DC group （P〈0.01）. DTH test showed that lysate-DC could prime T lymphocyte and elicit tumor antigen specific immune response, and over 80% mice in groups of lysate-DC showed obvious swelling in their foot pad. This response was strengthened with repeating inoculation, whereas DTH response was not seen in control group. In vivo depletion of NK cells resulted in a 40-60% reduction in growth suppression within the primary tumor, and depletion of CD4^＋ cells resulted in a 20% reduction in growth suppression. Conclusion： The minor lysate-pulsed dendritic cells vaccine could elicit antitumor activity in RM-1 loaded C57BL/6 mice, and prolong the duration of RM-1 loaded C57BL/6 mice. So DC-based immunotherapy with hormone-refractory prostate carcinoma yielded protective immunity, generated efficient cellular antitumor responses, thereby providing further preclinical support for feasible immunotherapy approaches for prostate cancer.
基金supported by the Medical and Health Technology Development Project of Shandong Province,China(No.2014WS0351)
文摘Objective： Professional antigen-presenting dendritic cells （DCs） and cytokine-induced killer （CIK） cells, components of anti-cancer therapy, have shown clinical benefits and potential to overcome chemotherapeutic re- sistance. To evaluate whether DC-CIK cell-based therapy improves the clinical efficacy of chemotherapy, we reviewed the literature on DC-CIK cells and meta-analyzed randomized controlled trials （RCTs）. Methods： We searched several databases and selected studies using predeflned criteria. RCTs that applied chemotherapy with and without DC-CIK cells separately in two groups were included. Odds ratio （OR） and mean difference （MD） were reported to measure the pooled effect. Results： Twelve reported RCTs （826 patients）, which were all performed on Chinese patients, were included. Combination therapy exhibited better data than chemotherapy： 1-year overall survival （OS） （OR=0.22, P〈0.01）, 2-year OS （OR=0.28, P〈0.01）, 3-year OS （OR=0.41, P〈0.01）, 1-year disease-free survival （DFS） （OR=0.16, P〈0.05）, 3-year DFS （OR=0.32, P〈0.01）, objective response rate （ORR） （OR=0.54, P〈0.01）, and disease control rate （DCR） （OR=0.46, P〈0.01）. Moreover, the levels of CD3＋ T-lymphocytes （MD=-11.65, P〈0.05） and CD4＋ T-lymphocytes （MD=-8.18, P〈0.01） of the combination group were higher. Conclusions： Immunotherapy of DC-CIK cells may enhance the efficacy of chemotherapy on solid cancer and induces no specific side effect. Further RCTs with no publishing bias should be designed to confirm the immunotherapeutic effects of DC-CIK cells.
