title: [Intravesical anchoring of streptavidin-tagged interleukin-4 fusion protein for immunotherapy of mouse superficial bladder cancer].
abstract: OBJECTIVE
  To evaluate the antitumor efficacy of streptavidin-tagged interleukin-4 (IL-4-SA) bifunctional fusion protein in the immunotherapy of mouse model of superficial bladder cancer.
  
  
  METHODS
  IL-4-SA fusion protein was prepared and its biological activity was determined. One day after MB49 cell implantation, 100 µl of 1 mg/ml NHS-PEO4-biotin was instilled into the bladder for 30 minutes, followed by intravesical instillation of 100 µl PBS, GFP-SA+IL-4 or IL-4-SA and incubation for 1 hour. The bladder irrigation was performed twice a week for three weeks. The CTL cytotoxicity and profile of CD8(+) tumor-infiltrating lymphocytes were analyzed.
  
  
  RESULTS
  The IL-4-SA fusion protein was durably anchored to the biotinylated mucosal surface of bladder wall for up to 5 days.On day 80 after the implantation of MB49 cells, all of PBS-treated mice died, and 8 out of 10 mice in the GFP-SA-treated group died from tumor burden.In contrast, 5 out of 10 mice in the IL-4-SA-treated group were tumor-free. The MB49 tumor-specific cytotoxicity from mice in the IL-4-SA group was (11.3 ± 1.2)%, (22.7 ± 1.5)% and (31.0 ± 3.0)% at the effector to target ratios of 1:1, 25:1 and 50:1, respectively. But the corresponding cytotoxicity was (4.3 ± 0.6)%, (9.0 ± 1.0)% and (14.3 ± 1.5)% in the GFP-SA+IL-4 group, and (3.3 ± 0.6)%, (7.3 ± 0.6)%, (12.7 ± 2.1)% in the PBS group. The tumor-specific cytotoxicity in the SA-CD40L group was significantly higher than that in the control groups (P < 0.05). The infiltrating CD8(+) T cells in tumors in the IL-4-SA-treated group were increased compare with those in other groups.
  
  
  CONCLUSIONS
  Intravesical anchoring of IL-4-SA elicites strong and long-lasting immunoprotection against superficial bladder cancer, and the novel immunotherapy may be an attractive therapeutic alternative in future.
authors.affiliation: Institute of Biotherapy, Southern Medical University, Guangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiao-ling
authors.initials: XL
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Jin-long
authors.initials: JL
authors.lastname: Li
authors.forename: Zhi-ming
authors.initials: ZM
authors.lastname: Hu
authors.forename: Ji-min
authors.initials: JM
authors.lastname: Gao
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D019921:Biotinylation; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015847:Interleukin-4 / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000627:therapeutic use; D019809:Streptavidin / Q000378:metabolism / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000628:therapy*
chemical_list: D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D019809:Streptavidin