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Comparison of the Fibronectin-binding Ability and Antitumor Efficacy of Various Mycobacteria¹

Division of Urological Surgery and Department of Medicine and Microbiology and Immunology, Washington University and The Jewish Hospital of St. Louis, St. Louis, Missouri 63110

Although the mechanism by which Bacillus Calmette-Guerin (BCG) exerts an antitumor effect on superficial bladder tumors is not fully understood, recent evidence has implicated binding of BCG organisms to fibronectin (FN) as requisite for this antitumor efficacy. Various substrains of BCG and other mycobacteria were tested in vitro for their relative capacities to bind both matrix and soluble FN. A substrain of Mycobacterium kansasii, designated the "high-binding strain," was found to bind FN more readily (P < 0.05) in in vitro studies, when compared to commercially available substrains of BCG (Tice, Connaught, and Armand Frappier). The binding by the three commercial strains of BCG to FN in vitro appeared to be equivalent. The high-binding strain was further demonstrated to attach more readily in vivo to the acutely injured murine bladder (P < 0.005) than the Armand Frappier substrain. Finally, using the MB49 murine bladder tumor model, an enhanced antitumor effect (P < 0.05) was noted in mice treated with intravesical high-binding strain, in comparison to the Armand Frappier substrain, during five weekly treatments. It appears not only that the commercial substrains of BCG bind FN in an equivalent manner but also that the relative binding capacities of the substrains correlate directly with antitumor activity. A substrain of M. kansasii appears to have been identified which may prove more clinically effective than the currently available strains of BCG.

¹ This work was supported by USPHS Grant CA 37926-04, CA42 487-01, and CA 44426-01 from the National Cancer Institute.

² Recipient of an American Foundation for Urological Disease Scholarship July 1988 to June 1990. To whom requests for reprints should be addressed; at Division of Urologic Surgery, Washington University, 216 Wohl, 4960 Audubon Avenue, St. Louis, MO 63110.

Received 9/11/89. Revised 3/23/90.

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