Effect of intravenous B.C.G. in guineapigs and pertinence to cancer immunotherapy in man.
Intravenous injection of heat-killed or irradiated B.C.G into tuberculin-positive guineapigs produced macroscopic lesions in the lung when examined 10 days or 4 or 6 weeks later. Microscopically, granulomas typical of a delayed hypersensitivity reaction were seen. Intravenous B.C.G. in normal guineapigs did not produce lesions. At equivalent doses to the killed vaccine, viable vaccine caused only mild lesions. Liver lesions were also found on early examination but by 4 weeks had almost resolved. Acid/alcohol-fast bacteria were only rarely detected. Purified portein derivative did not produce lesions, and antihistamine treatment did not modify the results. These results suggest that B.C.G. should be given by the intravenous route for cancer immunotherapy in man with great caution, especially in tuberculin-sensitive persons. The guineapig observations stress that hypersensitisation is a potential complicating feature of cancer immunotherapy, and this is discussed in the light of published clinical experience of B.C.G. by various routes. It is concluded that B.C.G. vaccines with a high proportion of viable organisms are to be preferred.