Therapeutic effect of intratumoral injection of BCG and other substances in rats and mice

Abstract

The experimental treatment of a rat sarcoma (McFiFi 2) by intratumoral injection of BCG2 is described. Tumors which have a mean diameter of less than 10 mm at the beginning of treatment are fully susceptible to BCG, although spontaneous regression is not observed at this stage. The effective dose of living BCG ranges from two injections of 0.1 mg to two injections of 1 mg, given IT at an interval of 7 days. The permanent cure of a proporation of the tumors may also be induced by IT injection of a similar dose of heat-killed BCG or of MER, or of 10(9) heat-killed C. parvum, according to the same schedule. Preimmunization of the rats with living BCG does not improve the efficiency of heat-killed BCG. Direct contact between the therapeutic material and the tumor cells is critical. If rats are grafted with two pieces of the same tumor in widely separated sites, the intratumoral treatment of only one of these tumors with living BCG is sufficient to induce regression of both tumors in 50% of the animals. The effect of BCG is counteracted by injection of silica or by ingestion of polaramine. The same intratumoral treatment with living BCG was applied to different rat and mouse tumors. Only McFiFi 2 tumors were cured by intralesional BCG. C3H mouse plasmocytoma 5563 was not cured by intratumoral BCG but its growth could be prevented by mixing BCG and tumor cells at the time of grafting; this tumor was considered to be of medium susceptibility. However, until there is definite proof that the two mechanisms are identical, one should consider the regression and cure of a growing tumor, and the prevention of tumor growth, as two different phenomena. The clinical treatment of human tumors resembles the first experimental procedure more closely than the second.