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Sequential Cytokine-Induced Killer Cell Immunotherapy Enhances the Efficacy of the Gemcitabine Plus Cisplatin Chemotherapy Regimen for Metastatic Nasopharyngeal Carcinoma.

Li Y, Pan K, Liu LZ, Li YQ, Gu MF, Zhang H, Shen WX, Xia JC, Li JJ - PLoS ONE (2015)

Bottom Line: The evaluation of long-term efficacy showed that the progression-free survival (PFS) rate was significantly higher in the GC+CIK group (log-rank test; p = 0.009), as was the overall survival (OS) rate (p = 0.006).In conclusion, sequential CIK treatment may be effective in enhancing the therapeutic efficacy of GC chemotherapy for metastatic NPC patients.This study provides a basis for alternative therapeutic strategies for metastatic NPC.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China; Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.

ABSTRACT
In this study, we investigated the efficacy of sequential cytokine-induced killer cell (CIK) immunotherapy with gemcitabine plus cisplatin (GC) regimen chemotherapy in metastatic nasopharyngeal carcinoma (NPC) patients. Between September 2006 and April 2010, 222 NPC patients with distant metastasis after radiotherapy completion were retrospectively analyzed: 112 patients received 4-6 cycles of GC chemotherapy at 4-week intervals, followed by at least 4 cycles of CIK immunotherapy at 2-week intervals (GC+CIK group); the remaining 110 patients received 4-6 cycles of GC chemotherapy alone (GC group). The evaluation of long-term efficacy showed that the progression-free survival (PFS) rate was significantly higher in the GC+CIK group (log-rank test; p = 0.009), as was the overall survival (OS) rate (p = 0.006). In conclusion, sequential CIK treatment may be effective in enhancing the therapeutic efficacy of GC chemotherapy for metastatic NPC patients. This study provides a basis for alternative therapeutic strategies for metastatic NPC.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of GC chemotherapy plus CIK treatment in metastatic NPC patients.All patients underwent 4–6 cycles of gemcitabine plus cisplatin regimen chemotherapy (GC chemotherapy) at 4-week intervals; over 2weeks later, a group of 112 patients received sequential treatment with autologous cytokine-induced killer cells (CIKs) for at least 4 cycles at 2-week intervals.
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pone.0130620.g002: Schematic diagram of GC chemotherapy plus CIK treatment in metastatic NPC patients.All patients underwent 4–6 cycles of gemcitabine plus cisplatin regimen chemotherapy (GC chemotherapy) at 4-week intervals; over 2weeks later, a group of 112 patients received sequential treatment with autologous cytokine-induced killer cells (CIKs) for at least 4 cycles at 2-week intervals.

Mentions: CIK cells were prepared as previously described [11,12,17]. Briefly, more than 2 weeks after the last GC chemotherapy, 50 ml of heparinized peripheral blood was collected from patients. Mononuclear cells were isolated by Ficoll density-gradient centrifugation and cultured using complete medium containing 1000 U/mL IFN-γ (Clone-gamma, Shanghai Clone Company, Shanghai, China) for 24 h. Mouse anti-human CD3 monoclonal antibody (R&D Systems, Shanghai, China), IL-2 (rhIL-2; Beijing Sihuan, Beijing, China) and IL-1α (Life Technologies, Guangzhou, China) were then added to a final concentration of 100 ng/ml, 1000 U/ml and 100 U/ml, respectively. Every 2–3 days, half of the medium was replaced with fresh complete medium containing 1000 U/ml IL-2 and cell density was maintained at 2 ×106 cells/ml. After approximately 14 days of culturing, autologous CIK cells were harvested. Prior to administration, the CIK cells were assessed for viability by the dye exclusion test and checked twice for possible contamination by bacteria, fungi, and endotoxin. For administration, harvested CIK cells were washed and re-suspended with 100 ml of normal saline containing 3–5 ml of 20% human serum albumin. The autologous CIK cells were then administered via intravenous infusion over 30 min. During transfusion, vital signs such as pulse, heart rate, breathing rate, blood pressure and temperature were monitored and recorded. Maintenance CIK treatment was given every 2 weeks with at least 4 cycles performed in each patient. The treatment procedure is shown in Fig 2. If cases were classified by medical imaging as complete remission (CR), partial remission (PR) or stable disease (SD), the maintenance CIK treatment continued. However, if PD was detected or patients refused to continue participation, CIK treatment was discontinued and an alternative therapy was recommended by physicians.


Sequential Cytokine-Induced Killer Cell Immunotherapy Enhances the Efficacy of the Gemcitabine Plus Cisplatin Chemotherapy Regimen for Metastatic Nasopharyngeal Carcinoma.

Li Y, Pan K, Liu LZ, Li YQ, Gu MF, Zhang H, Shen WX, Xia JC, Li JJ - PLoS ONE (2015)

Schematic diagram of GC chemotherapy plus CIK treatment in metastatic NPC patients.All patients underwent 4–6 cycles of gemcitabine plus cisplatin regimen chemotherapy (GC chemotherapy) at 4-week intervals; over 2weeks later, a group of 112 patients received sequential treatment with autologous cytokine-induced killer cells (CIKs) for at least 4 cycles at 2-week intervals.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476660&req=5

pone.0130620.g002: Schematic diagram of GC chemotherapy plus CIK treatment in metastatic NPC patients.All patients underwent 4–6 cycles of gemcitabine plus cisplatin regimen chemotherapy (GC chemotherapy) at 4-week intervals; over 2weeks later, a group of 112 patients received sequential treatment with autologous cytokine-induced killer cells (CIKs) for at least 4 cycles at 2-week intervals.
Mentions: CIK cells were prepared as previously described [11,12,17]. Briefly, more than 2 weeks after the last GC chemotherapy, 50 ml of heparinized peripheral blood was collected from patients. Mononuclear cells were isolated by Ficoll density-gradient centrifugation and cultured using complete medium containing 1000 U/mL IFN-γ (Clone-gamma, Shanghai Clone Company, Shanghai, China) for 24 h. Mouse anti-human CD3 monoclonal antibody (R&D Systems, Shanghai, China), IL-2 (rhIL-2; Beijing Sihuan, Beijing, China) and IL-1α (Life Technologies, Guangzhou, China) were then added to a final concentration of 100 ng/ml, 1000 U/ml and 100 U/ml, respectively. Every 2–3 days, half of the medium was replaced with fresh complete medium containing 1000 U/ml IL-2 and cell density was maintained at 2 ×106 cells/ml. After approximately 14 days of culturing, autologous CIK cells were harvested. Prior to administration, the CIK cells were assessed for viability by the dye exclusion test and checked twice for possible contamination by bacteria, fungi, and endotoxin. For administration, harvested CIK cells were washed and re-suspended with 100 ml of normal saline containing 3–5 ml of 20% human serum albumin. The autologous CIK cells were then administered via intravenous infusion over 30 min. During transfusion, vital signs such as pulse, heart rate, breathing rate, blood pressure and temperature were monitored and recorded. Maintenance CIK treatment was given every 2 weeks with at least 4 cycles performed in each patient. The treatment procedure is shown in Fig 2. If cases were classified by medical imaging as complete remission (CR), partial remission (PR) or stable disease (SD), the maintenance CIK treatment continued. However, if PD was detected or patients refused to continue participation, CIK treatment was discontinued and an alternative therapy was recommended by physicians.

Bottom Line: The evaluation of long-term efficacy showed that the progression-free survival (PFS) rate was significantly higher in the GC+CIK group (log-rank test; p = 0.009), as was the overall survival (OS) rate (p = 0.006).In conclusion, sequential CIK treatment may be effective in enhancing the therapeutic efficacy of GC chemotherapy for metastatic NPC patients.This study provides a basis for alternative therapeutic strategies for metastatic NPC.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China; Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.

ABSTRACT
In this study, we investigated the efficacy of sequential cytokine-induced killer cell (CIK) immunotherapy with gemcitabine plus cisplatin (GC) regimen chemotherapy in metastatic nasopharyngeal carcinoma (NPC) patients. Between September 2006 and April 2010, 222 NPC patients with distant metastasis after radiotherapy completion were retrospectively analyzed: 112 patients received 4-6 cycles of GC chemotherapy at 4-week intervals, followed by at least 4 cycles of CIK immunotherapy at 2-week intervals (GC+CIK group); the remaining 110 patients received 4-6 cycles of GC chemotherapy alone (GC group). The evaluation of long-term efficacy showed that the progression-free survival (PFS) rate was significantly higher in the GC+CIK group (log-rank test; p = 0.009), as was the overall survival (OS) rate (p = 0.006). In conclusion, sequential CIK treatment may be effective in enhancing the therapeutic efficacy of GC chemotherapy for metastatic NPC patients. This study provides a basis for alternative therapeutic strategies for metastatic NPC.

No MeSH data available.


Related in: MedlinePlus