Tumor Regression Mediated by Mycobacterium bovis (Strain BCG). Effects of Isonicotinic Acid Hydrazide, Cortisone Acetate, and Antithymocyte Serum

Abstract

A methylcholanthrene-induced murine sarcoma, which grows progressively when grafted intradermally into syngeneic mice, failed to grow when injected intradermally in admixture with BCG. The effect of BCG on tumor suppression depended on the number of BCG organisms injected: 10⁷ colonyforming units (CFU) suppressed the growth of 5×10₅ tumor cells in 100% of mice, 10₆ CFU suppressed the growth of 5×10₅ tumor cells in 50% of mice. Elimination of the ability of BCG organisms to multiply by heat treatment in vitro or isonicotinic acid hydrazide treatment in vivo did not influence the local tumor suppressive effect of BCG or interfere with the development of delayed hypersensitivity to purified protein derivative (PPD) of tuberculin. Cortisone acetate and antimouse thymocyte serum treatment abolished BCG-mediated tumor regression and temporarily impaired delayed hypersensitivity to PPD. The data suggest that immunologically committed small lymphocytes are essential for BCG-mediated tumor killing and that the time required for completion of BCG-mediated tumor killing is >7 days.