An analysis of the factors allowing promotion (rather than inhibition) of tumour growth by Corynebacterium parvum

Abstract

The following factors were found to determine whether C. parvum (CP) treatment promoted rather than inhibited the growth of methylcholanthrene-induced fibrosarcoma cells injected into CBA mice. (1) The dose of tumour cells. Promotion occurred only with low doses, around the TD50. (2) The route of injection of CP. Greater promotion was caused by intravenous (IV) than by subcutaneous (SC) administration. Addition of irradiated tumour cells to SC CP resulted in tumour inhibition. (3) The dose of CP. Promotion increased with increasing dose of either SC or IV CP. (4) The time of CP injection relative to tumour challenge. Promotion only occurred when CP was given before tumour cells, except when using IV CP and very few tumour cells. With increasing doses of tumour cells, first post-treatment with IV CP and then pre-treatment became inhibitory. The effect of CP on established immunity to tumour cells was also studied. Mice were immunized by tumour amputation. The resistance to tumour challenge thus generated could be abrogated by CP given before challenge, most effectively by a high dose IV. The data are interpreted according to the following hypothesis. (1) CP suppresses the expression of cell-mediated immunity to tumour antigens. (2) This is caused by trapping of anti-tumour effector cells at the site of CP deposition. (3) Promotion can only occur when CP is given before effector cells have reached the tumor site.