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Cancer Immunology, Immunotherapy

, Volume 57, Issue 4, pp 573–579 | Cite as

The fibronectin attachment protein of bacillus Calmette-Guerin (BCG) mediates antitumor activity

  • Haley W. Sinn
  • Bennett D. Elzey
  • Robert J. Jensen
  • Xiuqin Zhao
  • Weicheng Zhao
  • Timothy L. RatliffEmail author
Original Article

Abstract

Purpose

The receptor responsible for the attachment of bacillus Calmette-Guerin (BCG) to fibronectin, fibronectin attachment protein (FAP), has been cloned. Studies targeting FAP as an inducer of immunity in mycobacterial infections suggest that FAP is a highly immunogenic protein. In light of these findings and the need to find effective alternatives to BCG treatment for bladder cancer, we tested the ability of FAP to induce antitumor activity.

Materials and methods

The ability of FAP to bind to bladder tumor cells and the bladder wall was established using 125I-FAP. For testing antitumor activity in vivo, mice were catheterized and 5 × 104 MB-49 bladder tumor cells were implanted orthotopically on day 0. Test groups were treated with PBS only, FAP, or BCG on day 1 and day 8. A subset of mice was preimmunized with FAP prior to treatment.

Results

FAP was observed to bind to bladder tumor cells in a fibronectin-dependent manner. Attachment of FAP within the bladder followed the pattern established for BCG binding. Antitumor studies showed a significant reduction in tumor growth in FAP-treated mice that had been preimmunized with FAP. Tumor growth was not inhibited in naïve mice treated with FAP. Dose-response studies showed that FAP-induced antitumor activity is dose dependent, and experiments comparing BCG with FAP showed equivalent antitumor effects. In vitro experiments showed antigen-specific lymphocyte proliferation and a cytokine profile indicative of Th-1 polarization of the FAP-induced immune response. CD8+ T cells and natural killer cells were found to be required for the FAP-induced antitumor response.

Conclusions

FAP is an effective antitumor agent that inhibits tumor growth at a level equivalent to that observed for BCG. This protein may thus provide an alternative to BCG for treatment of superficial bladder cancer.

Keywords

Antitumor Activity Bladder Tumor Superficial Bladder Cancer Intravesical Instillation Naive Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Haley W. Sinn
    • 1
  • Bennett D. Elzey
    • 1
  • Robert J. Jensen
    • 1
  • Xiuqin Zhao
    • 2
  • Weicheng Zhao
    • 3
  • Timothy L. Ratliff
    • 1
    Email author
  1. 1.Department of UrologyUniversity of IowaIowa CityUSA
  2. 2.The Michael E. DeBakey VA Medical CenterHoustonUSA
  3. 3.University of Texas MD Anderson Cancer CenterHoustonUSA

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