Autologous CIK cell immunotherapy in patients with renal cell carcinoma after radical nephrectomy

Abstract

Objective: To evaluate the efficacy of autologous cytokine-induced killer (CIK) cells in patients with renal cell carcinoma (RCC).

Methods: 20 patients diagnosed with TNM stage I or II RCC were randomly divided into two groups, a CIK cell treatment group and a control group. The endpoint was progression-free survival (PFS) evaluated by Kaplan-Meier analyses.

Results: CD3(+), CD3(+)/CD8(+), CD3(+)/CD4(+), and CD3(+)/CD56(+) levels increased after CIK cell culture (P < 0.01). The median PFS in CIK cell treatment group was significantly longer than that in control group (PFS, 32.2 months versus 21.6 months; log-rank, P = 0.032), all patients were alive during the course of followup, and there are no statistically significant differences between two groups in OS (log-rank, P = 0.214). Grade III or greater adverse events were not observed.

Conclusions: CIK cells treatment could prolong survival in patients with RCC after radical nephrectomy and showed acceptable curative effect with potential enhancement of cellular immune function. This trial is registered with Clinicaltrials.gov NCT01799083.

Figures

Figure 1

(a) Trials and treatments of the two groups sectionalization. (b) Treatment protocol: cytokine-induced killer (CIK) cell transfusion cycle. Peripheral blood mononuclear cells (PBMCs) were cultured for 14 days in the presence of recombinant human interferon gamma (rhIFN-γ), recombinant human interleukin-2 (rhIL-2), and anti-CD3 monoclonal antibody before transfusion for two consecutive days. Patients were injected with rhIL-2 subcutaneously at 1 mU/day for 10 days immediately after transfusion for 10 days. Thymopentin was injected intramuscularly for 7 days before the next PBMC collection and culturing.

Figure 2

Phenotype analysis of cells from patients and detection of CIK cells and leukemic markers by FACS analysis. All cell samples for phenotype analysis were stained with FITC-conjugated antibodies against CD4, PE-conjugated antibodies against CD8, and APC-conjugated antibodies against CD56. (a) Typical phenotype analysis of PBMCs and CIK cells from CIK cell treatment group patient 7. (b) Comparison of the phenotype analyses of PBMCs and CIK cells. Phenotype comparisons were performed in samples from 10 patients who received CIK cell treatment, and the results were expressed as means ± SD. (c) Lymphocyte culture (PBMC and CIK). (A) PBMCs before isolation, induction and culture; some T lymphocytes can be seen in the peripheral blood. (B) After isolation, induction, and culture, lymphocytes become larger.

Figure 3

Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Left figure: PFS. Blue line: CIK cell treatment group. Red line: control group. Log-rank: P = 0.032. Right figure: OS. Blue line: CIK cell treatment group. Red line: control group. Log-rank: P = 0.214; all patients were alive during the course of followup, and there were no statistically significant differences between two groups in OS.

Figure 4

Example of chest CT before and after CIK cell treatment. ((a)–(c)) Images from Unique Patient Number (UPN) 7, who was diagnosed with pulmonary metastasis after radical nephrectomy and before CIK cell treatment. ((d)–(f)) Images from the same patient after two courses of CIK cell treatment. (a) A solid space-occupying lesion (0.9 × 1.2 cm) was observed in the left lung. (b) A circular lesion (0.5 × 0.5 cm) with high density and clear boundary was observed in the right lung. The CT value was 22 Hu in the plain scan. (c) The image shows a space-occupying lesion (1.1 × 0.9 cm) with a high density signal and a clear boundary. (d) After two courses of CIK cell treatment, the tumor burden in the inferior lobe of the left lung was significantly reduced (compared to the corresponding image in (a)). (e) Chest CT indicated almost complete absence of lesions in the left lung corresponding to the image shown in (b). (f) Shrinking of lung metastatic lesions was noted.