Enhanced antitumor effects and improved immune status of dendritic cell and cytokine‐induced killer cell infusion in advanced cancer patients

Overall Survival

Overall Survival

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Summary

The study aims to evaluate the efficacy of of DC-CIK cell treatment in patients with advanced cancer. Little progress has been made in the treatment of advanced cancer and Dendritic Cells (DCs) plus cytokine-induced killer (CIK) cells have exhibited antitumor effects. This method of immunotherapy was found to improve the imbalance in the immune system and prolong the OS in patients with advanced cancer.

Patients characteristics

90 patients aged 18-85 years old with advanced cancer were recruited in the present study. A total of 57 patients underwent DC-CIK immunotherapy (DC-CIK group) and 33 patients were administered BSC alone (BSC group). All the patients had a definitive histological or cytological diagnosis and were unresponsive or intolerant to conventional anticancer treatments, such as surgery, chemotherapy or radio- therapy. All patients must chemoradiotherapy-free for ≥3 months, with expected survival duration of >3 months, ECOG performance status of 0-2, with no cardiac arrhythmias, congestive heart failure or severe coronary artery disease, no active autoimmune disease or T-cell lymphoma; and no pregnancy or lactation.

Methodology

Preparation of DC and CIK cells
Peripheral blood mononuclear cells (PBMCs) were mobilized by granulocyte colony‐stimulating factor (G‐CSF) until WBC ≥10,000/μl, lymphocytes + monocytes ≥15%. Apheresis was performed from the patients using the COBE Spectra cell separator and repeated until ≥4.5×106/kg CD34+ cells were collected. PBMCs were separated by the Ficoll-Hypaque centrifugation method and incubated for 2 hours, and the adherent cells were cultured in vitro to generate autologous DCs in the presence of IL-4, tumor necrosis factor-α and granulocyte-macrophage (GM)-CSF. For the culture of autologous CIKs, PBMCs were cultured in AIM-V medium containing the recombinant cytokines IL-2, IFN-γ and monoclonal anti-human CD3 antibody (50 ng/ml). The cells were incubated in a humidified atmosphere with 5% CO2 at 37 ̊C. IL‐2 and IFN‐γ were added to the medium every 5 days.

Treatment

Patients in the control group received BSC alone, which included active symptom control, pain management, and the multi professional attention to the individual’s overall physical, psychosocial, spiritual and cultural needs. Patients in the DC-CIK group received autologous DC-CIK cells with an interval of 1 month in addition to BSC. For each cycle of treatment, the patients received three intravenous infusions of DC-CIK cells with 1-day intervals. Patients without disease progression were eligible for maintenance treatment. For each cycle of treatment, the patients received a median of 6.47×108 (range, 5.35×107-2.98×109) of autologous DC cells and 7.35×109 (range, 3.00-17.25×109) of CIK cells. The median number of CIK cell immunotherapy cycles was 2 (range, 1-13 cycles).

Results

Comparison of the changes in T‐cell subsets between the DC‐CIK and BSC groups
The changes in the T-cell subsets in peripheral blood between the DC-CIK and BSC groups we observed. The T-cell subsets were analyzed prior to and 1 month after the first treatment in patients from the two groups. Although no significant difference in the T-cell subsets were observed between the two groups at the beginning of the first treatment, the CD3+, CD3+/CD8+, CD8+/CD28+ and CD3+/CD56+ T-cell subsets were significantly increased in the DC‐ CIK group compared with the BSC group, while the CD8+/CD28- subset decreased significantly. No significant differences in the CD3+/CD4+ and CD4+/CD25+ subsets were observed between the two groups before and after treatment. Thus, these data indicated that DC-CIK cell treatment improved cellular immune function in advanced cancer patients.
Association between OS and T‐cell subset changes
Demonstrates that a lower CD8+/CD28- and a higher of CD8+/CD28+ ratio may be associated with longer OS. In addition, DC-CIK treatment administration, age (>60 vs. <60 years), clinical stage and the frequency of CIK treatment significantly affected the OS of patients in the DC-CIK group.
Side effects
No severe side effects were observed during DC-CIK cell treatment. Three patients in the DC-CIK group developed fever (<38.5 ̊C) that was spontaneously relieved 2 hours after the infusion. No other serious adverse events, such as high fever, chills, rash or hemolytic anemia, were reported in patients receiving DC-CIK cell treatment.

Conclusion

This data presented herein demonstrated that T-cell subset changes were associated with the OS of advanced cancer patients, while DC-CIK cell immunotherapy may regulate and enhance the host’s immune function, significantly improving the OS of patients with advanced cancer.

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Scientific article publishing date :7/20/2017

Immucura identifier BSC21_227EN

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