Efficacy analysis of triple-negative breast cancer patients treated with dendritic cell-cytokine-induced killer cell immunotherapy

Overall Survival

Overall Survival

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Summary

The study investigates the efficacy of dendritic cell-cytokine-induced killer (DC-CIK) cell immunotherapy combined with chemotherapy with or without radiotherapy for triple-negative breast cancer (TNBC) patients following
surgery. The results suggest the patients may benefit from an adjuvant infusion of DC-CIK cells concurrent with conventional therapy to prevent disease relapse and improve OS.

Patients characteristics

67 patients with histologically confirmed triple-negative breast cancer who underwent surgery and received chemotherapy with or without radiotherapy. Twenty-five patients were assigned to the DC-CIK group and 42 patients were assigned to the non-DC- CIK group or the control group.

Methodology

Generation of CIK cell and DC
Percoll density gradient centrifugation was performed to isolate peripheral blood mononuclear cells (PBMCs) from 50 mL heparinized whole blood samples. The lymphocytes were collected, plated at a concentration of 2×106 into 75 cm2 culture flasks and incubated under 5% CO2 at 37°C. After 1-2 h, complete GT-T551 medium supplemented with 50 ng/ mL interleukin-4 (IL-4) and 100 ng/ mL granulocyte-macrophage colony-stimulating factor (GM-CSF) was added to each culture flask. The medium was replenished every 3 days. On day 5, the medium was supplemented with 500 U/mL tumor necrosis factor-α (TNF-α) and 100 μg/mL WT1 antigen. Mature tumor antigen pulsed DCs were harvested at day 7.
The suspended cells that were previously collected were transferred to a 75 cm2 culture flask that was pre- coated with 50 μg (5 μg/mL) CD3 monoclonal antibody. On day 1, complete GT-T551 medium supplemented with interferon (IFN)-1000 U/mL and 1000 U/mL IL-2 was added to adjust the cell density to 5×106 cells/mL. Every 3 days, the cells received fresh medium containing IL-2 (500 U/mL). On day 7, the CIK cells were mixed with tumor antigen-pulsed DCs at a ratio of 1:10. The mixed DC-CIK cells were maintained in complete GT-T551 medium supplemented with IL-2 (500 U/mL).

Treatment

Chemotherapy with or without radiotherapy treatment
All of the TNBC patients underwent four 21-day cycles of anthracyline and paclitaxel-based chemotherapy after surgery. Intravenous administration of epirubicin (60 mg/m2) was performed on day 1, followed by a 3-h intravenous infusion of 175 mg/m2 paclitaxel on day 2. Patients with lymph node metastasis or dis- tant metastasis received sequential intensity- modulated radiation therapy before finishing their chemotherapy regimen, with irradiation of 50 Gy/25f applied outside the axillary +/- lymphatic drainage area. The tumor bed received 10-16 Gy.
DC-CIK treatment scheduleThe DC-CIK cells were then administered at 2-5×109 cells a day for 4 days via intravenous infusion during the intervals of chemotherapy. One cycle was defined as four transfusions, and it included 1-2×1010 cells. The interval of each cycle extended over at least 14 days.

Results

Adverse effects of DC-CIK cell transfusions
Among the patients who underwent DC-CIK cell transfusions, one patient (4%) experienced a mild fever and chills, while another patient experienced an allergic reaction, anaphylactic shock, hypotension, and chest tightness. Both patients recovered with symptomatic treatment. None of the patients in the cohort exhibited problems with hepatic or renal function.
Assessment of KPS scores
The baseline KPS scores for the DC-CIK and non-DC-CIK groups were 87.6±5.97 and 86.07±5.70, respectively (P=0.53). After treatment, the KPS scores for the two groups were 83.02±4.32 and 72.67±5.01, respectively (P<0.05). OS and DFS estimates
Kaplan-Meier estimates of 3-year DFS rates for the DC-CIK and non-DC-CIK groups were significantly improved, and the 5-year DFS rates for the DC-CIK and non-DC- CIK groups were improved from 20.08% to 39.32%, although it only approached statistical significance.
The 3-year DFS rate and 5-year DFS rate for the advanced-stage group (which included TNM stages IIB, III, and IV), was significantly affected by DC-CIK treatment. The 3-year OS rate was also significantly improved for the advanced-stage group. Although compared with non- DC-CIK group, the improvement of 5-year OS rate with DC-CIK treatment in the advanced- stage subgroup had only borderline statistical significance, the 5-year OS rate was still improved from 22.72% to 41.56%.

Conclusion

Advanced TNM stage TNBC patients may benefit from an adjuvant infusion of DC-CIK cells concurrent with conventional therapy to prevent disease relapse and improve OS.

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Scientific article publishing date 12/30/2019

Immucura identifier BSC21_265EN

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