Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy with Cytokine-Induced Killer Cells Improves Survival in Gastric and Colorectal Cancer Patients

Abstract

Gastric and colorectal cancers (GC and CRC) have poor prognosis and are resistant to chemo- and/or radiotherapy. In the present study, the prophylactic effects of dendritic cell (DC) vaccination are evaluated on disease progression and clinical benefits in a group of 54 GC and CRC patients treated with DC immunotherapy combined with cytokine-induced killer (CIK) cells after surgery with or without chemo-radiotherapy. DCs were prepared from the mononuclear cells isolated from patients using IL-2/GM-CSF and loaded with tumor antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3–5 times in 2 weeks as one cycle with a total of 188.3±79.8×106 DCs and 58.8±22.3×108 CIK cells. Cytokine levels in patients' sera before and after treatments were measured and the follow-up was conducted for 98 months to determine disease-free survival (DFS) and overall survival (OS). The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients. By Cox regression analysis, DC/CIK therapy reduced the risk of post-operative disease progression (p<0.01) with an increased OS (<0.01). These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients.

Anti-tumor activity of dendritic cell-cytokine induced killer cells (DC-CIKs) sensitized to HER2 against HER-positive breast cancer cells

“…In the co-culture system of DC-CIK, antigen-sensitized DCs and CD4+T cells interact to activate CD8+T cells. As these cells co-incubate with tumor cells, they result in stronger anti-tumor activity as compared with CIKs (Gao et al, 2014;Han et al, 2014). The detection of IFN-γ and IL-12 levels in the co-cultured supernatant also further demonstrates that CIKs activated by anchored antigensensitized DCs secrete more IFN-γ and IL-12 than the control groups, promoting anti-tumor activity (Palucka and Banchereau, 2013;Li et al, 2014).…”

Immunotherapy of DC-CIK cells enhances the efficacy of chemotherapy for solid cancer: a meta-analysis of randomized controlled trials in Chinese patients

“…Fever (1), arrest of bone-marrow, gastrointestinal reactions, peripheral neurotoxicity DcRen2013B (Ren et al, 2013) Vomiting (1), diarrhea (1), hepatic complications (2) Neuritis (1), vomiting (9), diarrhea (12), hepatic complications (4) DcYuan2013L (Yuan et al, 2013) Anemia, skin petechiae, fatigue, oral pain, constipation, peripheral neuropathy Fever, anemia, skin petechiae, fatigue, oral pain, constipation, peripheral neuropathy DcNi2013B (Ni et al, 2013) None Fever (3) DcGao2014G (Gao et al, 2014) None Fever (9) None: no adverse effects and reporting standards, which will benefit patients on condition that there is more registration (Schmeel et al, 2014). Meta-analysis is an optimal choice to analyze dozens of clinical studies.…”

“…Only two of twelve studies focused on breast cancer (Ren et al, 2013;Ni et al, 2013) and most items excepting ORR and DCR were available only in one study (Ni et al, 2013). CD4 + , CD4 + /CD8 + , and DCR of NSCLC and 3-year OS of gastrointestinal cancer were also extracted from one study (Gao et al, 2014). Other comparisons were performed in at least two RCTs.…”

Identification of a protein associated with the activity of cytokine‑induced killer cells

“…The cells were cultured at 37˚C with 5% CO 2 until the 11th day. The CIK protein was extracted as reported by Gao et al (14) with certain modifications. The CIKs were centrifuged at 150 x g for 10 min at 4˚C, and the precipitate was washed with 1 ml 0.9% physiological saline three times.…”