Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients

• Published in: PloS one Vol. 9; no. 4; p. e93886
• Main Authors: Gao, Daiqing, Li, Changyou, Xie, Xihe, Zhao, Peng, Wei, Xiaofang, Sun, Weihong, Liu, Hsin-Chen, Alexandrou, Aris T, Jones, Jennifer, Zhao, Ronghua, Li, Jian Jian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Aged; Analysis; Antibodies; Antigen (tumor-associated); Antigens; Biology and Life Sciences; Breast cancer; Cancer; Cancer therapies; Cancer Vaccines - therapeutic use; Care and treatment; CD3 antigen; Cell survival; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Cytokine-Induced Killer Cells - immunology; Cytokines; Dendritic cells; Dendritic Cells - immunology; Development and progression; Disease Progression; Disease-Free Survival; Drug therapy; Female; Gastric cancer; Granulocyte-macrophage colony-stimulating factor; Health aspects; Health risks; Hospitals; Humans; Immunology; Immunotherapy; Immunotherapy - methods; Interferon; Interleukin 12; Interleukin 2; Killer cells; Leukocytes (mononuclear); Lung cancer; Lymphocytes; Lymphoma; Lymphomas; Male; Medicine and Health Sciences; Metastasis; Middle Aged; Oncology; Patient outcomes; Patients; Peripheral blood; Physiological aspects; Prognosis; Prostate cancer; Radiation therapy; Regression analysis; Research and Analysis Methods; Stem cells; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Stomach Neoplasms - therapy; Studies; Surgery; Survival; Survival Rate; T cell receptors; Treatment Outcome; Tumors; Vaccination; γ-Interferon; Sacramento California; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0093886

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 × 10(6) DCs and 58.8 ± 22.3 × 10(8) 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.