Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy
Abstract
:1. Introduction
1.1. Activation Receptors: NKG2D, DNAM-1, CD56 and NKp30
1.2. Inhibitory Receptor
1.3. Fas-Mediated Apoptosis
2. Gastrointestinal Tumors
2.1. Hepatocellular Carcinoma
2.2. Immunotherapy with CIK Alone or in Combination with DC as Adjuvant Therapy After Resection or RFA
2.3. Immunotherapy with CIK Alone or in Combination with DC in Combination with TACE (Palliative)
2.4. Gastric Cancer
2.5. Colorectal Liver Metastases
2.6. Pancreatic Cancer
3. Lung Cancer
4. Breast Cancer
4.1. Classification and Therapy of Breast cancer
4.2. Meta-Analysis and Stage IV Breast Cancer with the Follow-up Time Up to 10 Years
5. Glioblastoma
6. Renal Cell Carcinoma
7. Hematological Diseases
8. Future Perspectives
9. Conclusions
Funding
Conflicts of Interest
References
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Study Reference | Patients (n) Total | Patients (n) Treated with CIK Cells | Therapy | Results | Conclusions |
---|---|---|---|---|---|
Takayama et al. (2000) [34] | 150 | 76 | Resection; Immunotherapy group: additional infusions of lymphocytes activated in vitro with rIL-2 and anti-CD3 | Better recurrence-free in immunotherapy group; no differences in OS between the two groups | CIK cell therapy can improve recurrence-free outcomes after surgery |
Hao et al. (2010) [39] | 146 | 72 | TACE; Immunotherapy group: additional i.v. CIK cell transfusions | Improved PFS and OS in TACE plus CIK cell therapy group | Adjuvant immunotherapy with CIK cells improve the efficacy of TACE in HCC patients |
Wang et al. (2012) [40] | 95 | 48 | TACE/RFA; Immunotherapy group: additional CIK cell transfusions | Significantly longer DFS in CIK cell plus TACE with RFA group; no significant difference for OS | Recurrence can be controlled by CIK infusion combined with TACE and RFA |
Lee et al. (2015) [41] | 230 | 115 | TACE/RFA or percutaneous ethanol injection PEI Immunotherapy group: additional i.v. CIK cell transfusions | RFS and OS significantly better in immunotherapy group; no significant for severe adverse events between the two groups | CIK cells can prevent recurrence and improve survival in combination with surgical resection, RFA or percutaneous ethanol injection |
Event | No. of Trials | No. pts | Before-CIK | Mean Difference | 95% CI | p Value | Heterogeneity |
---|---|---|---|---|---|---|---|
CD3+ | 9 | 359 | 359 | 8.21 | 5.79 to 10.64 | <0.00001 | 67% |
CD4+ | 5 | 174 | 174 | 5.59 | 4.10 to 7.07 | <0.0001 | 0% |
CD3+CD8+ | 4 | 174 | 174 | 2.55 | −2.46 to 7.56 | 0.32 | 89% |
CD4+CD8+ | 4 | 144 | 144 | 0.49 | 0.37 to 0.61 | <0.00001 | 53% |
CD3+CD56+ | 6 | 222 | 222 | 7.80 | 2.61 to 12.98 | 0.003 | 99% |
NK | 4 | 154 | 154 | 6.21 | 2.25 to 10.17 | 0.002 | 90% |
CD8+ | 5 | 174 | 174 | -2.75 | −3.88 to −1.63 | <0.00001 | 0% |
Treg | 3 | 153 | 153 | -1.26 | −1.94 to −0.58 | 0.0003 | 58% |
Study Reference | RCTs (n) Total | Patients (n) Total | Therapy |
---|---|---|---|
Wang et al. (2014) [57] | 17 | 1172 | Chemotherapy; Immunotherapy group: additional CIK cell and DC cell transfusions |
Mi et al. (2016) [60] | 10 | Chemotherapy; Immunotherapy group: additional CIK cell transfusions and IL-2 | |
Xiao et al. (2018) [64] | 16 | 1197 | Radiotherapy; Immunotherapy group: additional CIK cell and DC cell transfusions |
Total | 43 | 2369 |
Study Reference | RCTs (n) Total | Patients (n) Total | Therapy |
---|---|---|---|
Wang et al. (2014) [68] | 633 | CIK cell therapy alone, DC cell therapy alone and CIK and DC combination | |
Hu et al. (2017) [70] | 11 | 914 | Chemotherapy; Immunotherapy group: additional CIK cell and DC cell transfusions |
Total | 11 | 1547 |
Study Reference | RCTs (n) Total | Patients (n) Total | Therapy | CR | PR | ORR | DCR | PD |
---|---|---|---|---|---|---|---|---|
Wang et al., 2017, [81] | 12 | 594 | Chemotherapy; | OR = 2.71 CI = 1.60–4.58 p = 0.0002 | OR = 1.49 CI = 1.01–2.20 p = 0.04 | OR = 2.77 CI = 1.88–4.10 p < 0.00001 | OR = 2.90 CI = 1.72–4.90 p < 0.0001 | OR = 0.34 CI = 0.20–0.58 p < 0.0001 |
Immunotherapy group: additional CIK cell and DC cell transfusions | ||||||||
Bader, 2016, [82] | 1 | 40 | Chemotherapy; | n.a | n.a | n.a. | n.a. | n.a. |
Immunotherapy group: additional IL-15 activated CIK cell transfusions | ||||||||
Total | 13 | 634 |
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Garofano, F.; Gonzalez-Carmona, M.A.; Skowasch, D.; Schmidt-Wolf, R.; Abramian, A.; Hauser, S.; Strassburg, C.P.; Schmidt-Wolf, I.G.H. Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy. Int. J. Mol. Sci. 2019, 20, 4307. https://doi.org/10.3390/ijms20174307
Garofano F, Gonzalez-Carmona MA, Skowasch D, Schmidt-Wolf R, Abramian A, Hauser S, Strassburg CP, Schmidt-Wolf IGH. Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy. International Journal of Molecular Sciences. 2019; 20(17):4307. https://doi.org/10.3390/ijms20174307
Chicago/Turabian StyleGarofano, Francesca, Maria A. Gonzalez-Carmona, Dirk Skowasch, Roland Schmidt-Wolf, Alina Abramian, Stefan Hauser, Christian P. Strassburg, and Ingo G. H. Schmidt-Wolf. 2019. "Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy" International Journal of Molecular Sciences 20, no. 17: 4307. https://doi.org/10.3390/ijms20174307