BCG preparations, cultured homogeneously dispersed or as a surface pellicle, elicit different immunopotentiating effects but have similar antitumor activity in a murine fibrosarcoma

Abstract

Four preparations of Bacillus Calmette-Guerin (BCG), cultured either homogeneously dispersed or as a surface pellicle, were compared with reference to their immunomodulating capacities and antitumor effects. The BCG preparations included two vaccines that originated from the same seed strain, but one had subsequently been produced in each way. The immunological assays included in vivo stimulation of lymph nodes in a mouse model, in vitro stimulation of murine spleen lymphocytes, and in vivo stimulation of macrophages in a Listeria monocytogenes clearance model in the mouse. The antitumor effect was determined in a non-immunogenic, non-metastasizing murine fibrosarcoma. The results indicated that vaccines produced as a homogeneous culture in general induced a higher lymphocyte stimulation both in vivo and in vitro. In the Listeria clearance model a markedly enhanced clearance was established with three of the four preparations, the phenomenon being related to the number of culturable particles administered. This difference was not attributed to the production method, but to other factors, including the actual composition of the vaccine. The results found in the immunological assays were not connected to the observed antitumor activities, as for each preparation a combination of route, dose, and time interval for tumor regression was found. Prophylactic administration of BCG had no effect at all; enhancement was observed after intratumoral administration of the two preparations prepared as surface pellicles. It is concluded that a protocol for the quality control of bacterial vaccines used for cancer immunotherapy should include both immunological assays and a range of different animal tumor models.