title: Combined therapy with cytokine-induced killer cells and oncolytic adenovirus expressing IL-12 induce enhanced antitumor activity in liver tumor model.
abstract: Both adoptive immunotherapy and gene therapy hold a great promise for treatment of malignancies. However, these strategies exhibit limited anti-tumor activity, when they are used alone. In this study, we explore whether combination of cytokine-induced killer (CIK) adoptive immunotherapy with oncolytic adenovirus-mediated transfer of human interleukin-12 (hIL-12) gene induce the enhanced antitumor potency. Our results showed that oncolytic adenovirus carrying hIL-12 (AdCN205-IL12) could produce high levels of hIL-12 in liver cancer cells, as compared with replication-defective adenovirus expressing hIL-12 (Ad-IL12). AdCN205-IL12 could specifically induce cytotoxocity to liver cancer cells. Combination of CIK cells with AdCN205-IL12 could induce higher antitumor activity to liver cancer cells in vitro than that induced by either CIK or AdCN205-IL12 alone, or combination of CIK and control vector AdCN205-GFP. Furthermore, treatment of the established liver tumors with the combined therapy of CIK cells and AdCN205-IL12 resulted in tumor regression and long-term survival. High level expression of hIL-12 in tumor tissues could increase traffic of CIK cells to tumor tissues and enhance their antitumor activities. Our study provides a novel strategy for the therapy of cancer by the combination of CIK adoptive immunotherapy with oncolytic adenovirus-mediated transfer of immune stimulatory molecule hIL-12.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.forename: Qianzhen
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Shan
authors.forename: Junjie
authors.initials: J
authors.lastname: Shen
authors.forename: Limei
authors.initials: L
authors.lastname: Liu
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Xia
authors.forename: Ping
authors.initials: P
authors.lastname: Bie
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Youhong
authors.initials: Y
authors.lastname: Cui
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000166:cytology / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication
chemical_list: D018664:Interleukin-12