Chemotherapy with or without autologous cytokine-induced killer cell transfusion as the first-line treatment for stage IV gastrointestinal cancer: a phase II clinical trial

Abstract

Objective: To investigate the efficacy of autologous cytokine-induced killer (CIK) cell therapy combined with chemotherapy versus chemotherapy alone for the treatment of stage IV gastrointestinal (GI) cancer in the first-line setting.

Methods: Thirty-three patients diagnosed with stage IV GI cancer were divided into chemotherapy plus CIK group (chemo-CIK, n = 16) and chemotherapy-alone group (chemo-alone, n = 17). Autologous peripheral blood mononuclear cells were separated by flow cytometry, cultured in vitro to induce CIK cells, and transfused into patients on days 14 and 16 of the first and second chemotherapy cycles.

Results: The median progression-free survival (PFS) was 5.6 months for patients in the chemo-CIK group and 3.83 months for those in the chemo-alone group. The difference was borderline significant (P = 0.06), indicating a potential advantage for combined CIK cell transfusion with chemotherapy in improving PFS. A favored objective response rate was also observed in the chemo-CIK group than in the chemo-alone group. This study also revealed that CIK cell transfusion restored the cellular immunity in these GI cancer patients. The percentage of natural killer T cells, NK cells, CD3(+) T cells, and T-cell subgroups CD4(+) proportion in the peripheral blood of cancer patients significantly increased after the CIK cell transfusion, while the change in T-cell subgroups CD8(+) and CD4(+)/CD8(+) did not differ significantly.

Conclusions: The study showed that the addition of CIK cell transfusion to traditional chemotherapy in the first-line setting was associated with a prolonged PFS and enhanced T-lymphocyte subset activity, supporting a potential treatment choice for advanced GI cancer patients.

Keywords: CIK cell; Chemotherapy; Clinical trial; Gastrointestinal cancer.

Fig. 1

Proliferation curve of cytokine-induced killer (CIK) cells. The proliferation fold of CIK cells increased rapidly from the 9th day and remained steady until the 15th day. Results are mean values of independent experiments performed in triplicate and with three trials

Fig. 2

Progression-free survival (PFS) (a) and overall survival (OS) (b) analysis of the two groups. The Kaplan–Meier method was employed to estimate the survival rates of the two groups. The median PFS was 5.6 months (95 % CI 4.1–7.2 months) for the patients in the chemo–CIK group and 3.83 months (95 % CI 3.0–4.7 months) for the patients in the chemo-alone group. The median OS was 13.9 months (95 % CI 10.1–17.7 months) for the chemo–CIK group and 11.0 months (95 % CI 8.5–13.5 months) for the chemo-alone group

Fig. 3

Serum tumor markers of the two groups before and after the treatment. *P < 0.01 (post-treated vs. before-treated)

Fig. 4

Phenotype characterization of cytokine-induced killer (CIK) cells. CIK cells cultured for 14 days were stained with human monoclonal antibodies including anti-CD3-FITC plus anti-CD56-PE (a), anti-CD4-FITC plus anti-CD8-PE (b), anti-CD4-PE plus anti-CD56-APC (c), and anti-CD8-PE plus anti-CD56-APC (d)