title: Cbl-b gene silencing in splenic T lymphocytes as a therapeutic strategy to target the prostate cancer RM-1 cell tumors in immune competent mice.
abstract: OBJECTIVE
  In recent years, the field of cancer immunotherapy has become a research hotspot and is currently faced with numerous challenges. The objective of this study was to assess the success of cbl-b gene silencing in splenic T lymphocytes as an immune strategy to target the murine prostate cancer RM-1 cells in vitro and solid tumors in vivo.
  
  
  METHODS
  For this purpose, cbl-b gene-specific siRNA was designed, synthesized, and was transfected into mouse splenic T lymphocytes, followed by assessment of T cell activation, TH1 cytokine production, and in vitro cytotoxicity against RM-1 cell targets. For in vivo cytotoxicity studies, first the RM-1 tumor model was established in immune competent mice that were later tumor-injected with splenic T lymphocytes transfected with specific shRNA for cbl-b gene silencing.
  
  
  RESULTS
  The data show that the cbl-b gene silencing in T lymphocytes resulted in an enhanced surface expression of CD69 activation marker, elevated production of interleukin (IL)-2 and interferon (IFN)-γ, and their increased cytotoxicity as effectors against RM-1 prostate cancer cells. The tumor injection with cbl-b shRNA-transfected T lymphocytes also resulted in significant reduction of the tumor size as compared with controls.
  
  
  CONCLUSIONS
  cbl-b gene silencing strategy enhanced the immune function of T lymphocytes, increased their cytotoxic potential against RM-1 prostate cancer cells, as well as caused significant suppression of the tumor growth in immune competent mice.
authors.affiliation: Department of Urology, The Affiliated School of Clinical Medicine of Xuzhou Medical College, Xuzhou Central Hospital, Xuzhou, China. bujiniao2008@qq.com.
authors.forename: Z-D
authors.initials: ZD
authors.lastname: Shi
authors.forename: X-F
authors.initials: XF
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Hao
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: Y-X
authors.initials: YX
authors.lastname: Wang
authors.forename: B-Z
authors.initials: BZ
authors.lastname: Dong
authors.forename: W-H
authors.initials: WH
authors.lastname: Chen
authors.forename: Z-G
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Y-M
authors.initials: YM
authors.lastname: Wang
authors.forename: Q
authors.initials: Q
authors.lastname: Fu
authors.forename: C-H
authors.initials: CH
authors.lastname: Han
authors.forename: S
authors.initials: S
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D050721:Proto-Oncogene Proteins c-cbl / Q000172:deficiency / Q000235:genetics*; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C118387:Cblb protein, mouse; D050721:Proto-Oncogene Proteins c-cbl