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Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients.

Gao D, Li C, Xie X, Zhao P, Wei X, Sun W, Liu HC, Alexandrou AT, Jones J, Zhao R, Li JJ - PLoS ONE (2014)

Bottom Line: The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3-5 times in 2 weeks as one cycle with a total of 188.3 ± 79.8 × 10(6) DCs and 58.8 ± 22.3 × 10(8) CIK cells.The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients.These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients.

View Article: PubMed Central - PubMed

Affiliation: Biotherapy Center, Qingdao Center Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao, China.

ABSTRACT
Gastric and colorectal cancers (GC and CRC) have poor prognosis and are resistant to chemo- and/or radiotherapy. In the present study, the prophylactic effects of dendritic cell (DC) vaccination are evaluated on disease progression and clinical benefits in a group of 54 GC and CRC patients treated with DC immunotherapy combined with cytokine-induced killer (CIK) cells after surgery with or without chemo-radiotherapy. DCs were prepared from the mononuclear cells isolated from patients using IL-2/GM-CSF and loaded with tumor antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3-5 times in 2 weeks as one cycle with a total of 188.3 ± 79.8 × 10(6) DCs and 58.8 ± 22.3 × 10(8) CIK cells. Cytokine levels in patients' sera before and after treatments were measured and the follow-up was conducted for 98 months to determine disease-free survival (DFS) and overall survival (OS). The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients. By Cox regression analysis, DC/CIK therapy reduced the risk of post-operative disease progression (p<0.01) with an increased OS (<0.01). These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients.

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Following up of DC/CIK therapy and control patients.The prognoses of patients were recorded up to 98 months after the dates of surgery in both treatment and control groups.
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pone-0093886-g001: Following up of DC/CIK therapy and control patients.The prognoses of patients were recorded up to 98 months after the dates of surgery in both treatment and control groups.

Mentions: Patients in the treatment group received one cycle of low dose chemotherapy starting on the day after mononuclear cells collection with Carmofure (100 mg, po., bid) for 5∼6 days. The infusion of DCs and CIK cells was started on day 2 or day 3 after chemotherapy. Prepared DC cells were divided into two parts: one part was mixed with CIK cells in 250 ml normal saline containing 1500 U/mL IL-2 and 1% albumin, and infused into the patients intravenously. The other part was suspended in 1.5 ml normal saline and injected subcutaneously into the area of draining lymph nodes adjacent to the tumor sites. The treatment was repeated 3–5 times in 2 weeks as one cycle. Patients with advanced stage diseases received 2 cycles of the treatment, while early stage patients were treated with one cycle. The immune responses of patients were monitored before and after the treatment by measuring serum levels of IFN-γ, IL-2, IL-6, IL-10, and IL-12 determined by ELISA (R&D systems, Minneapolis, MN, USA). The time schedules of DC and CIK preparation and infusion were shown in Figure 1.


Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients.

Gao D, Li C, Xie X, Zhao P, Wei X, Sun W, Liu HC, Alexandrou AT, Jones J, Zhao R, Li JJ - PLoS ONE (2014)

Following up of DC/CIK therapy and control patients.The prognoses of patients were recorded up to 98 months after the dates of surgery in both treatment and control groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3974849&req=5

pone-0093886-g001: Following up of DC/CIK therapy and control patients.The prognoses of patients were recorded up to 98 months after the dates of surgery in both treatment and control groups.
Mentions: Patients in the treatment group received one cycle of low dose chemotherapy starting on the day after mononuclear cells collection with Carmofure (100 mg, po., bid) for 5∼6 days. The infusion of DCs and CIK cells was started on day 2 or day 3 after chemotherapy. Prepared DC cells were divided into two parts: one part was mixed with CIK cells in 250 ml normal saline containing 1500 U/mL IL-2 and 1% albumin, and infused into the patients intravenously. The other part was suspended in 1.5 ml normal saline and injected subcutaneously into the area of draining lymph nodes adjacent to the tumor sites. The treatment was repeated 3–5 times in 2 weeks as one cycle. Patients with advanced stage diseases received 2 cycles of the treatment, while early stage patients were treated with one cycle. The immune responses of patients were monitored before and after the treatment by measuring serum levels of IFN-γ, IL-2, IL-6, IL-10, and IL-12 determined by ELISA (R&D systems, Minneapolis, MN, USA). The time schedules of DC and CIK preparation and infusion were shown in Figure 1.

Bottom Line: The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3-5 times in 2 weeks as one cycle with a total of 188.3 ± 79.8 × 10(6) DCs and 58.8 ± 22.3 × 10(8) CIK cells.The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients.These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients.

View Article: PubMed Central - PubMed

Affiliation: Biotherapy Center, Qingdao Center Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao, China.

ABSTRACT
Gastric and colorectal cancers (GC and CRC) have poor prognosis and are resistant to chemo- and/or radiotherapy. In the present study, the prophylactic effects of dendritic cell (DC) vaccination are evaluated on disease progression and clinical benefits in a group of 54 GC and CRC patients treated with DC immunotherapy combined with cytokine-induced killer (CIK) cells after surgery with or without chemo-radiotherapy. DCs were prepared from the mononuclear cells isolated from patients using IL-2/GM-CSF and loaded with tumor antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3-5 times in 2 weeks as one cycle with a total of 188.3 ± 79.8 × 10(6) DCs and 58.8 ± 22.3 × 10(8) CIK cells. Cytokine levels in patients' sera before and after treatments were measured and the follow-up was conducted for 98 months to determine disease-free survival (DFS) and overall survival (OS). The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients. By Cox regression analysis, DC/CIK therapy reduced the risk of post-operative disease progression (p<0.01) with an increased OS (<0.01). These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients.

Show MeSH
Related in: MedlinePlus