Table 1.
Clinical studies applying CIK cells for the treatment of RCC.
| Study | Number of Patients | Therapeutic Approach | Clinical Response | Adverse Event | Conclusion |
|---|---|---|---|---|---|
| Liu et al. [21] | 1 (1 RCC) | Modified auto-CIKs | Symptomatic improvement (relieved cough, dyspnea, chest distress and thoracalgia) and reduction of pleural fluid | Fever (~38 °C) but recovered 2 days later | The patient achieved partial success |
| Zhan et al. [26] | 137 (137 RCC) | Group 1: tumor lysate-pulsed DCs + auto-CIKs Group 2: IFN-α Group 3: no adjuvant therapy |
Increased CD4+/CD8+ ratio, decreased CD4+CD25high cells and significantly higher 3- and 5-year OS rates | Controllable fever and fatigue in DC-CIK group | Postoperative immunotherapy with tumor lysate-pulsed DC-CIK cells may prevent recurrence/metastasis and increase OS rates |
| Zhang et al. [20] | 40 (10 RCC) | Auto-CIKs | 6-month, 1-year and 3-year OS rates were 70.0, 60.0 and 57.5%, respectively; median OS was 34.9 months; 6 recurrence, 12 metastasis and 15 deaths in all patients (2 recurrence, 5 metastasis and 3 deaths in RCC) | Controllable fever and poor appetite | CIK cell therapy can be an effective adjuvant instrument of the routine anti-tumor treatment |
| Cui et al. [27] | 121 (7 RCC) | Tumor lysate-pulsed DCs + auto-CIKs | Improvements in the physical strength, appetite and sleeping status | Controllable fever, insomnia, anorexia, joint soreness and skin rashes | Tumor lysate-pulsed DC-CIK cells were safe without serious adverse side-effects |
| Zhang et al. [19] | 20 (20 RCC) | Group 1: auto-CIKs Group 2: control |
Significantly longer median PFS; 6 CR, 4 SD in CIK group and 5 CR, 3 SD, 2 PD in control group | Mild arthralgia, laryngeal edema, fatigue, and low-grade fever | CIK cell treatment could prolong survival in patients with RCC after radical nephrectomy |
| Wang et al. [28] | 28 (28 RCC) | GmDCs + auto-CIKs | 4 CR, 7 PR, 10 SD, 6 PD and 1 death | Flu-like symptoms with fever | DCR was significantly related with cycles of treatment |
| Wang et al. [24] | 29 (29 RCC) | Auto-CIKs + IL-2 | 4 PR, 18 SD and 7 PD; 1-year survival was 82.8%; median PFS and OS were 7.7 months and 12.6 months, respectively | Grade 1 and 2 fever and grade 2 diarrhea | Auto-CIKs can induce regression of RCC; MDSCs can serve as a potential marker for the prognosis of patients receiving a CIK-based therapy |
| Li et al. [22] | 20 (1 RCC) | RetroNectin-activated auto-CIKs + conventional therapies | 1 CR, 5 PR, 9 SD and 5 PD; median PFS and OS were 7.7 months and 12.6 months, respectively (1 CR with an OS of 14 months and PFS of 8 months in RCC) | Fever | RetroNectin-activated CIKs combined with conventional therapies could improve the prognosis of metastatic brain tumor patients |
| Zheng et al. [30] | 410 (410 RCC) | Group 1: tumor lysate-pulsed DCs + auto-CIKs Group 2: IFN-α |
Significantly increased 3-, 5-year OS rates and PFS in DC-CIK group | Transient low-grade fever and fatigue | Adjuvant DC-CIK treatment after surgery prolonged PFS and reduced mortality |
| Zhao et al. [29] | 122 (122 RCC) | In operable patients: Group 1: tumor lysate-pulsed DCs + auto-CIKs Group 2: control in inoperable patients: Group 1: auto-CIKs Group 2: control |
Significantly higher 3-year DFS and decreased risk of post-operative disease progression and relapse in operable patients; Significantly higher 3-year OS rate, median OS and PFS in inoperable patients | Flu-like symptoms such as fever and fatigue | DC-CIK cells might be more efficient and personalized for the patients with tumor resection, and CIK cells could improve the prognosis for inoperable patients |
| Yang et al. [32] | 1 (1 RCC) | Auto-CIKs + sorafenib | Metastasis remained stable | No serious adverse reactions | CIK cells combined with sorafenib could result in a synergistic effect |
| Mai et al. [33] | 34 (34 RCC) | Group 1: sunitinib/sorafenib monotherapy Group 2: DCs + auto-CIKs + sunitinib/sorafenib |
Significantly higher median PFS and 3-year OS rate; more SD and less PD and death | No serious adverse reactions in group 2; bone marrow suppression, oral ulcer, fatigue, and hand-foot syndrome | Sunitinib/sorafenib combined with CIK cells could significantly prolong the median PFS and 3-year OS |
| Wang et al. [35] | 2 (1 RCC) | Auto-CIKs + pembrolizumab | 1 CR (RCC) and 1 near-CR | No serious adverse reactions associated with CIK cells | Pembrolizumab in combination with CIK cells led to potent anti-tumor activity in RCC; CD3+ T cell infiltration in baseline tumor biopsies is a potential predictive biomarker |
| Chen et al. [34] | 37 (8 RCC) | DCs + auto-CIKs + pembrolizumab | 2 CR, 5 PR, 13 SD and 11 PD (1 CR, 1 PR, 4 SD, 2 PD in RCC); median OS and PFS were 270 and 162 days | All treatment-related adverse reactions were reversible or controllable; grade 3 or 4 toxicities, including fever and chills, were observed in two patients | Pembrolizumab-activated autologous DC-CIK cells were safe and effective in advanced solid tumors |
| Li et al. [31] | 228 (12 RCC) | Group 1: tumor lysate-pulsed DCs + auto-CIKs Group 2: tumor lysate-pulsed DCs + cytotoxic T cells |
Elevated percentage of CD3+ HLA-DR+ T cells, NK cells and cytokines such as IL-2, IL-6 in group 1; Elevated total CD3+ T cells, CD8+ T cells, CD3+ HLA-DR+ cells and IL-12 in group 2 | -- | DCs combined with cytotoxic T cells have more dominance to induce Th1 cytokine response instead of skewing toward the Th2 cytokine profile |
Auto-CIKs: autologous CIK cells; DCs: dendritic cells; IFN-α: interferon-α; OS: overall survival; PFS: progression-free survival; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; gmDCs: genetically modified dendritic cells; DFS: disease-free survival; DCR: disease control rate; IL-2: interleukin-2; MDSCs: myeloid-derived suppressor cells.