Mechanism of action of BCG-tumor cell vaccines in the generation of systemic tumor immunity. I. Synergism between BCG and line 10 tumor cells in the induction of an inflammatory response.

The intradermal injection of a vaccine composed of 10(7) X-irradiated, syngeneic hepatocarcinoma line 10 (L10) cells admixed with 10(8) Mycobacterium bovis strain BCG into inbred Sewall Wright strain 2 guinea pigs induced a local acute and then chronic inflammatory response. Cellular analysis of enzymatically dispersed dermal vaccination sites and regional lymph nodes revealed quantitative differences between the cellular infiltrate induced by a mixed BCG-tumor cell vaccine and the inflammation induced by either 10(8) BCG alone or 10(7) tumor cells alone. Analysis of dermal sites from days 1 through 4 following vaccination showed that sites receiving the BCG-tumor cell vaccine contained twofold to fourfold more cells than did those induced by BCG alone and more than fourfold the number of cells induced by L10 cells alone. These results indicated that there was a synergistic interaction between BCG and L10 cells in the induction of an inflammatory response at the site of vaccination. Analysis of the superficial distal axillary lymph nodes draining the site of vaccination revealed a similar synergistic interaction between BCG and L10, such that lymph nodes draining vaccination sites had a greater total cellular content than that induced by either BCG or L10 cells administered separately. When two other tumors, also syngeneic to strain 2 guinea pigs, were tested for their ability to interact synergistically with BCG to elicit an inflammatory response, it was found that the antigenically distinct hepatocarcinoma line 1 tumor also shared this characteristic with L10, whereas the L2C B-cell leukemia did not.