Retrospective analysis of the efficacy of adjuvant CIK cell therapy in epithelial ovarian cancer patients who received postoperative chemotherapy

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Summary

Cytokine-induced killer (CIK) cells are demonstrated to hold potent cytolytic effect against ovarian cancer cells in vitro and in vivo. However, the clinical efficacy of maintenance therapy of CIK cells in patients with epithelial ovarian cancer (EOC) after first-line treatment is still unclear. The data suggests that adjuvant CIT with CIK cells is an effective therapeutic approach to prolonging the survival of EOC patients.

Patients characteristics

646 patients with histologically confirmed epithelial ovarian cancer (EOC). The average age was 57.94 years (± 10.80 years), with a range of 34–89 years. Among them, 72 patients that underwent surgery/chemotherapy and received postoperative immunotherapy were enrolled as the CIT group, whereas 574 cases that underwent surgery/chemotherapy only were enrolled as the control group.

Methodology

CIK cell preparation
50 mL of heparinized peripheral blood was obtained from the EOC patient over 2 weeks after the patient had completed chemotherapy treatment and when routine blood examination results had normalized. Peripheral blood mononuclear cells were separated by Ficoll–Hypaque density centrifugation, resuspended at 2 × 106 cells/mL in fresh serum-free X-VIVO 15 medium containing 1,000 U/mL recombinant human IFN-γ and incubated at 37 °C in a humidified atmosphere containing 5% CO2 for 24 hours. Subsequently, 100 ng/mL mouse-anti-human CD3 monoclonal antibody, 100 U/mL recombinant human IL-1 and 1,000 U/mL recombinant human IL-2 were added to the media. Finally, 100 ng/mL mouse anti-human CD3 monoclonal antibody, Fresh IL-2 and fresh medium were added every 2 days and the cell density was maintained at 2 × 106 cells/mL. The CIK cells were harvested on the 14th day. A fraction of harvested CIK cells were taken for viability and phenotype analysis, and the majority of fresh CIK cells were transfused intravenously (IV) into the patients immediately upon harvesting.

Treatment

All patients underwent completion surgery/surgical staging or comprehensive staging and cytoreduction. Following surgery, all patients in the control and CIT groups received three-six cycles of chemotherapy with a TP regimen (paclitaxel and cisplatin), TC regimen (paclitaxel and carboplatin), CAP (cyclophosphamide, epirubicin and cisplatin), or CBP regimen (cyclophosphamide, carboplatin, and Bleomycin). Beginning one month after completion of chemotherapy, CIT-group patients were subject to immune cell infusions every 2 weeks.
CIK treatment
Patients received CIK (range 8.0 × 109 – 1.3 × 1010 cells) via intravenous infusion during each cycle. Patients received at least four cycles of CIK cell transfusion, and the interval of every cycle was 2 weeks. The patients were eligible for maintenance treatment if they were disease-stable.

Results

Toxicity
Across all processes of CIK cell immunotherapy in the CIT group, 12.5% (9/72) of patients developed self- limiting light fevers and shivering at grade 1 or 2. No patients exhibited pulmonary or renal symptoms, or any sign of infection, hepatic functional deterioration, or autoimmune disorders.
Overall survival (OS) and progression-free survival analysis (PFS)
All 646 patients enrolled in this study were firstly assessed for OS. Over a median follow-up of 33.0 months (range, 8 – 127 months), 47.1% (304/646) of patients died with a median post-surgery OS of 43.67 months (range 0.37–120.9 months). The OS rates at 1-, 3-, and 5-years were 87%, 63% and 47% for CIT patients, and 65%, 44%, and 31% for control group patients, respectively. Patients who received adjuvant CIT exhibited a significantly more favorable OS than control group patients (median OS, 63.6 vs. 39.6 months).

Conclusion

These data indicate that adjuvant CIT with CIK cells is an effective therapeutic approach to prolonging the survival of EOC patients.

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Scientific article publishing date 11/11/2018

Immucura identifier BSC21_282EN

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