A randomized controlled trial on patients with or without adjuvant autologous cytokine- induced killer cells after curative resection for hepatocellular carcinoma

Overall Survival

Overall Survival

CONTACT US

Summary

The study aims to investigate the safety and efficacy of Autologous cytokine-induced killer (CIK) cells therapy on patients with hepatocellular carcinoma (HCC). The findings suggest that the therapy was safe and effective to prolong the median TTR in patients with HCC after curative resection.

Patients characteristics

200 patients histologically diagnosed with hepatocellular carcinoma ages >18 years old, with stage BALC A or B with tumor number. All the patients had no prior to anticancer therapy, with Eastern Cooperative Oncology Group performance status (ECOG) 0 or 1, with adequate bone marrow, liver and renal function.

Methodology

All patients are divided into two groups, CIK group (n=100) and control group (n=100) with allocation ratio of 1:1.
Preparation of the cell
50 mL of heparinized peripheral blood were obtained from the patients after two weeks of surgery. The PBMCs were separated by Ficoll-Hypaque density centrifugation, resuspended in fresh serum-free X- VIVO 15 medium containing 1,000 U/mL interferon (IFNg) at 2×106 cells/mL and incubated at 37C in a humidified atmosphere containing 5% CO2 for 24 hours. Then, 100 ng/mL mouse anti-human CD3 monoclonal antibody, 100 U/mL Interleukin-1a (IL-1a) and 1,000 U/mL human recombinant IL-2 (rhIL-2) were added. Cell growth was observed daily. Fresh medium containing IL-2 was added every two days to maintain a cell concentration of 2 to 4×106 cells/mL.On day 14, cells were harvested, washed, and resuspended with 100 mL of normal saline containing 1% of human serum albumin. Then, the autologous CIK was transfused through a vein within 60 min after harvest.

Treatment

Patients in the CIK group were scheduled to receive four cycles of autologous CIK infusions with the dose of each cycle range from 1×1010 to 1.5×1010 cells and total dose of each patient is range from 4×1010 to 6×1010 cells within 3 months after liver resection. The first CIK infusion was performed within six weeks after surgery. The patients received CIK infusions intravenously in an upper limb at each cycle. The interval between cycles was about two weeks.

Results

Time of recurrence
No patients were detected to have any residual tumor at the post-operative 4th-week assessment. Recurrence was diagnosed in 85 patients, with 40 patients in the CIK group and 45 patients in the control group, respectively (40% vs. 45%). The median TTR of the CIK group was 13.6 months (IQR 6.5–25.2 mo) vs. 7.8 months (IQR 2.7–17.0 mo) of the control group. There was a 74% improvement in median TTP for the patients in the CIK group.
Disease-free survival (DFS) and overall survival (OS)The one-, three-, and five- year DFS were 83.8%, 59.9%, and 51.8% in the CIK group, and 69.9%, 55.9%, and 44.9% in the control group, respectively.The one-, three-, and five- year OS were 91.7%, 82.2%, and 69.3% in the CIK group, and 87.0%, 76.3%, and 56.2% in the control group, respectively.
Safety
Neither hospital death nor serious adverse events occurred in the whole cohort. The overall incidence of treatment-related complications was 11.8% in the CIK group and 14.7% in the control group. All adverse events were of grade 1 or 2. Fever was reported in eight (7.9%) patients who received CIK, and five (4.9%) of them had transient recurring fever after each cycle of CIK infusion. The fever was self-limiting. No infection or allergic reaction was observed in the patients who received CIK.

Conclusion

In summary, this study showed that CIK as an adjuvant treatment prolonged the TTR in patients with hepatocellular carcinoma (HCC), CIK was safe, with no significant toxicity.

Article Reference link: click here

Scientific article publishing date 31/3/2016

Immucura identifier BSC21_036EN

ALL SCIENTIFIC PAPERS
CONTACT US