title: Superior anti-tumor protection and therapeutic efficacy of vaccination with dendritic cell/tumor cell fusion hybrids for murine Lewis lung carcinoma.
abstract: BACKGROUND
  The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research into their potential use in immunotherapy in the treatment of cancer. In this study, we examined the efficacy of dendritic cell-tumor cell fusion hybrid vaccines in eliciting an immune response against Lewis lung carcinoma (LLC) cells, as compared to other types of tumor vaccines. In addition, we also tested whether the efficacy of the vaccines was affected by the route of administration. Four different tumor vaccines were compared: (1) HC (hybrid cell), consisting of DC/LLC hybrids; (2) DC+LLC (DCs pulsed with apoptotic LLCs); (3) DC without antigen loading/pulsing; (4) LLC (apoptotic/irradiated tumor cells). We also compared four different routes of administration for each vaccine: (1) Preimmunization; (2) Vaccination therapy; (3) Adoptive immunotherapy; (4) Vaccination therapy combined with adoptive immunotherapy. Anti-tumor immunity was assessed in vivo and the CTL (cytotoxic T lymphocyte) response as well as the expression of key cytokines, IFN-γ and IL-10 were further evaluated using in vitro assays.
  
  
  RESULTS
  Our data demonstrate that vaccination with HC hybrids provides more effective anti-tumor protective immunity and significantly greater therapeutic immunity than vaccination with DC+LLC, DC or LLC. Most remarkably, vaccination therapy with HC hybrids was more successful than combination (vaccination + adoptive) therapy for the induction of anti-tumor responses. Splenocytes harvested from mice immunized with HC hybrids demonstrated the greatest cytotoxic T lymphocyte (CTL) activity and their production of IFN-γ was high, while their production of IL-10 was very low.
  
  
  CONCLUSIONS
  Our results suggest that vaccination therapy with DC-tumor cell fusion hybrids provides more effective protection against lung cancer.
authors.affiliation: Department of Cancer Biotherapy Center and.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Chen
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Liu
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Huang
authors.forename: Ruilei
authors.initials: R
authors.lastname: Li
authors.forename: Hongqing
authors.initials: H
authors.lastname: Zhang
authors.forename: Suwei
authors.initials: S
authors.lastname: Dong
authors.forename: Chunlei
authors.initials: C
authors.lastname: Ge
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Xue
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Song
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006822:Hybrid Cells / Q000276:immunology* / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D051379:Mice; D047368:Tumor Burden
chemical_list: D019496:Cancer Vaccines