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

被引:88
作者
Gao, Daiqing [1 ]
Li, Changyou [1 ]
Xie, Xihe [1 ]
Zhao, Peng [1 ]
Wei, Xiaofang [1 ]
Sun, Weihong [1 ]
Liu, Hsin-Chen [2 ]
Alexandrou, Aris T. [2 ]
Jones, Jennifer [3 ]
Zhao, Ronghua [3 ]
Li, Jian Jian [2 ]
机构
[1] Qingdao Univ, Coll Med, Affiliated Hosp 2, Qingdao Ctr Hosp,Biotherapy Ctr, Qingdao 266071, Peoples R China
[2] Univ Calif Davis, NCI Designated Comprehens Canc Ctr, Dept Radiat Oncol, Sacramento, CA 95817 USA
[3] Univ Saskatchewan, Dept Med, Saskatoon, SK S7N 0W0, Canada
关键词
SIPULEUCEL-T; ACTIVE IMMUNOTHERAPY; IMMUNE-RESPONSE; PHASE-I; VACCINATION; PEPTIDE; ANTIGEN; CHEMOTHERAPY; LYMPHOMA; ENHANCE;
D O I
10.1371/journal.pone.0093886
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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-gamma, 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 +/- 79.8x10(6) DCs and 58.8 +/- 22.3x10(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-gamma 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.
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页数:9
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