Aim： To investigate the antitumor immunity by a dendritic cell （DC） vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods： DC from bone marrow of C57BL/6 were trans...Aim： To investigate the antitumor immunity by a dendritic cell （DC） vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods： DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine （SLC） cDNA by Lipofectamine2000 liposome and tumor lysate. Total RNA extracted from SLC＋lysate-DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction （RT-PCR）. The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. Results： We found that in the prostate tumor model of C57BL/6 mice, the adminstration of SLC＋lysate-DC inhibited tumor growth most significantly when compared with SLC-DC, lysate-DC, DC or phos- phate buffer solution （PBS） counterparts （P 〈 0.01）. Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4＋, CD8＋ T cell and CD11c＋ DC within established tumor treated by SLC＋lysate-DC vaccine than other DC vaccines （P 〈 0.01）. Conclusion： DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4＋, CD8＋ T cell and DC, which might provide a potential immunotherapy method for prostate cancer.展开更多
Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVa...Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac?, Dandrit Biotech,Copenhagen,Denmark). Imiquimod cream, proleukin and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFNg EliSpot. Secondary objectives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten vaccinations. Seven patients remained in stable disease (SD) three months after the first vaccination. After ten vaccinations (six months), four patients still showed SD and continued vaccinations on a monthly basis. These four patients received a total of 12, 16, 26 and 35 vaccinations, respectively. Five patients showed an unexpectedly prolonged survival. The treatment was well tolerated and only minor adverse events were reported. Quality of life did not change during the study period. In four of the seven patients with SD, vaccine-specific T cells were detected by IFNγ EliSpot assays, whereas only one patient with progressive disease (PD) showed vaccine-specific responses. Conclusion: This DC-based vaccine trial has indicated a correlation between vaccine-specific immunity and sustained SD. Furthermore, we observed an unexpectedly prolonged survival in some patients, which may indicate delayed effect of DC vaccination after completion of the treatment. A prospective randomized phase-IIb or -III is needed to further evaluate the use of MelCancerVac? vaccine treatment in patients with progressive NSCLC.展开更多
BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for ch...BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such antitumor activity can be increased using cell lysates derived from an honokioltreated cholangiocarcinoma cell line (KKU-213L5). AIM To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). METHODS The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. RESULTS Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. CONCLUSION The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.展开更多
文摘Aim： To investigate the antitumor immunity by a dendritic cell （DC） vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods： DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine （SLC） cDNA by Lipofectamine2000 liposome and tumor lysate. Total RNA extracted from SLC＋lysate-DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction （RT-PCR）. The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. Results： We found that in the prostate tumor model of C57BL/6 mice, the adminstration of SLC＋lysate-DC inhibited tumor growth most significantly when compared with SLC-DC, lysate-DC, DC or phos- phate buffer solution （PBS） counterparts （P 〈 0.01）. Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4＋, CD8＋ T cell and CD11c＋ DC within established tumor treated by SLC＋lysate-DC vaccine than other DC vaccines （P 〈 0.01）. Conclusion： DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4＋, CD8＋ T cell and DC, which might provide a potential immunotherapy method for prostate cancer.
文摘Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac?, Dandrit Biotech,Copenhagen,Denmark). Imiquimod cream, proleukin and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFNg EliSpot. Secondary objectives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten vaccinations. Seven patients remained in stable disease (SD) three months after the first vaccination. After ten vaccinations (six months), four patients still showed SD and continued vaccinations on a monthly basis. These four patients received a total of 12, 16, 26 and 35 vaccinations, respectively. Five patients showed an unexpectedly prolonged survival. The treatment was well tolerated and only minor adverse events were reported. Quality of life did not change during the study period. In four of the seven patients with SD, vaccine-specific T cells were detected by IFNγ EliSpot assays, whereas only one patient with progressive disease (PD) showed vaccine-specific responses. Conclusion: This DC-based vaccine trial has indicated a correlation between vaccine-specific immunity and sustained SD. Furthermore, we observed an unexpectedly prolonged survival in some patients, which may indicate delayed effect of DC vaccination after completion of the treatment. A prospective randomized phase-IIb or -III is needed to further evaluate the use of MelCancerVac? vaccine treatment in patients with progressive NSCLC.
基金the grant from the Thailand Research Fund,No.BRG6180010Naresuan University Research Grant,No.R2561B001
文摘BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such antitumor activity can be increased using cell lysates derived from an honokioltreated cholangiocarcinoma cell line (KKU-213L5). AIM To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). METHODS The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. RESULTS Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. CONCLUSION The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.
