IMMUNOTHERAPEUTIC TRIALS OF MURINE AND GUINEA-PIG SOLID TUMORS BY ORAL ADMINISTRATION OF BCG

Abstract
Efficacy of oral administration of BCG on the growth of various tumors in mice and guinea pigs was studied. The growth-inhibitory effect varied depending on the tumor systems and the experimental conditions. Weekly oral administrations with 5 mg doses of BCG to mice or 80 mg doses of BCG to guinea pigs were ineffective on syngeneic mouse melanoma B16 or syngeneic guinea pig hepatocarcinoma line-10 but effective on syngeneic mouse carcinoma IMC and syngeneic guinea-pig fibrosarcoma H9A. Oral BCG seemed effective also on allogeneic mouse Ehrlich carcinoma, developed with a relatively small size of tumor cell inoculum, and on guinea-pig syngeneic liposarcoma H10. On Ehrlich tumors, oral BCG given once/wk seemed to have better effects than did oral BCG given twice/wk or s.c. once or repeatedly; heat-killed BCG given orally showed no effect. However, it seems premature to draw a definite conclusion on the efficacy of oral BCG on Ehrlich and H10 tumors, because some of these tumors regressed spontaneously even in nontreated control animals. The host responses to oral BCG were studied with the following results. Weekly oral administrations with 80 mg doses of BCG to guinea pigs elicited positive skin reactions to 25 TU [tuberculin unit] PPD [purified protein derivative] in about 65 days after the 1st BCG, while a single s.c. injection of 8 mg of BCG did so within 10 days. Orally administered BCG organisms were recovered largely from Peyer''s patches, a little from the mesenteric lymph nodes, and very little from the liver and the spleen. The BCG distributive pattern was in reverse order when BCG was given s.c. Histologic examinations of Peyer''s patches indicated enlargement of germinal centers, in which primitive reticular cells proliferated prominently and the macrophages with tangible bodies scattered frequently.

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