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.

Evolutionary development of IgE and the role of anaphylactic-type reactions in resistance to solid tumours

“…Basophil infiltration has been reported in regressing tumours [23,42], and in our model relatively large quantities of histamine have been found in the tumours 1. Treatment with anti-histamines at non-immunosuppressive doses has inhibited the therapeutic effects of immunostimulants such as BCG or Corynebaeterium parvum on rat and mouse tumours [19,45]. Also consistent with our hypothesis is the recent observation [66] that inflammatory cells completely infiltrate regressing tumours whilst being relegated to the margins of progressors.…”

BCG treatment of human tumour xenografts in athymic nude mice

“…In previous work, growth of rat tumour xenografts was similarly controlled by admixture with BCG or C. parvum (Pimm & Baldwin, 1975, although the suippression in athymic mice was in accordance with that seen in syngeneic recipients, so that carcinogen-induced sarcomas and hepatomas were readily controlled, while only slight suppression (Chassoux & Salomon, 1975;Hopper et al, 1976;Moore & Nisbet, 1978;Keller, 1977). The indication from the present work is that locally activated host responses can similarly control growth of human malignant cells in an in vivo environment.…”

C. Parvum immunotherapy of transplanted rat tumours

“…The response is, however, totally abolished by systemic host treatment with a specific macrophage toxin, particulate silica. Comparable studies in this and other laboratories with BCG in the rat indicate that, with this agent too, tumour suppression by local application is dependent upon local activation of host macrophages, so that, while immunosuppression does not abolish the response (Pimm and Baldwin, 1 9 7 6~; Moore et al, 1975), depletion of host macrophages abrogates the effect Chassoux and Salomon, 1975).…”