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


METHODS
The ability of FAP to bind to bladder tumor cells and the bladder wall was established using (125)I-FAP. For testing antitumor activity in vivo, mice were catheterized and 5 x 10(4) 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.
Sinn
Haley W
HW
Department of Urology, University of Iowa, 3216 MERF, 375 Newton Road, Iowa City, IA 52242, USA.
Elzey
Bennett D
BD
Jensen
Robert J
RJ
Zhao
Xiuqin
X
Zhao
Weicheng
W
Ratliff
Timothy L
TL
D000818:Animals; D001500:BCG Vaccine / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology / Q000378:metabolism; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000628:therapy*