Adjuvant treatment for triple-negative breast cancer: a retrospective study of immunotherapy with autologous cytokine- induced killer cells in 294 patients

CIK treatment

CIK treatment

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Summary

The study aims to investigate the efficacy and safety of the combination of chemotherapy and cytokine-induced killer (CIK) for patients with triple-negative breast cancer (TNBC). The results show that the combinational treatment can be used to lower the relapse and metastasis rate and therefore extending the survival time.

Patients characteristics

294 patients with histologically diagnosed with TNBC as defined by the immunohistochemical staining feature of ER, PR, and HER2. All patients has no occurrence of distant metastasis prior to surgery, absence of other malignant tumor and with the Karnofsky performance status score higher than 70 %. Patients are divided into two groups, CIK group (n=147) and control group (n=147).

Methodology

CIK cells preparation
The patient peripheral blood mononuclear cells (PBMC) were then cultured in a medium containing 1000 U/mL interferon-γ(IFN-γ), 100 U/mL recombinant human interleukin-1α (IL-1α), and 50 ng/mL anti-CD3 antibody, with 5% CO2 at 37 °C for 24 hours, followed by the addition of 300 U/mL of recombinant human IL-2 to the medium. This medium was constantly replaced with a fresh medium containing IFN-γ and IL- 2 every 5 days. On the 14th day, the CIK cells were harvested. Eventually, over 5 × 109 of CIK cells with > 95% viability were obtained.

Treatment

All patients underwent modified radical mastectomy, radical mastectomy, or breast-conserving surgery. Postoperatively, all patients underwent 4 to 8 cycles of standard adjuvant chemotherapy.
In the CIK group, on day 15 and day 16 of each chemotherapy cycle, patients received an intravenous infusion of at least 5 × 109 CIK cells.

Results

Disease-free survival (DFS) rates of the CIK and control group after 1-, 3-, and 5- year intervals were 99.3% vs. 95.9%, 91.8% vs. 83.7%, and 88.1% vs. 81.3%, respectively.
The overall survival (OS) interval of the CIK group was significantly longer than that of the control group and the 1-, 3-, and 5- year OS rates of the CIK and control group were 99.3% vs. 98.0%, 96.6% vs. 91.8%, and 93.4% vs. 84.1%, respectively.
Side effects
Both groups experienced common adverse reactions, including myelosuppression, fever, nausea and vomiting, liver dysfunction, kidney dysfunction, and the peripheral nerve toxicity. The main adverse reactions were I to II degrees. In the III-IV-degree myelosuppression group, 11 were in the CIK group and12 in the control group; the side effects of the digestive tract were within the III degree; fever, renal impairment, and neurotoxicity were of I-II degrees. No intolerable adverse reactions were observed in both the groups.
There were no obvious adverse reactions observed during the injection of CIK cells. In the CIK group, 11 patients had a transient fever reaction (temperature < 38.5°C) that returned to normal condition within 24 hours after symptomatic treatment. Moreover, during the course of CIK cell treatment, no patient quit midway due to intolerant side effects.

Conclusion

This strategy of CIK cell therapy after adjuvant chemotherapy could reduce recurrence and metastasis in postoperative TNBC patients, thereby prolong the overall survival time with minimum side effects. Therefore, CIK cell immunotherapy could be a potential new strategy for systemic adjuvant therapy after surgery for TNBC patients in the near future.

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Scientific article publishing date 12/10/2018

Immucura identifier BSC21_251EN

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