BCG-induced protection against malignant melanoma: possible immunospecific effect in a murine system

Abstract

This report documents for the first time BCG-induced protection against a murine malignant melanoma. Adult Balb/C mice recieved 0.1-cm3 doses of BCG prior to intramuscular challenge with 1 x 10-6 S-91 melanoma cells. A 65% reduction in melanoma incidence was noted in BCG-pretreated mice. The possibility of specific protection induced by the BCG against the melanoma exists, since the BCG pretreatment did not protect against challenge with 1 x 10-5 mammary carcinoma cells or 1 x 10-4 MCA fibrosarcoma cells in the same strain of mice. Lack of immunogenicity was not a factor in the inability of the carcinoma and sarcoma to be inhibited by BCG. The strenght of the BCG-induced protection against the S-91 melanoma was demonstrated by significantly decreased tumor incidence following three different log challenge doses of the melanoma. However, reduction of the sarcoma challenge dose to as few as 10-2 cells administered to BCG pretreated mice did not result in decreased tumor incidence. It was further discovered that as few as two doses of 0.1 cm3 of BCG were sufficient to produce a 70% reduction in melanoma incidence compared with the incidence in control animals (P less than .001). Lymphocyte-mediated cytotoxicity studies paralleled the results of the in vivo experiments. Lymphocytes immune to each of the three tumors showed significant cytotoxicity against their respective tumor target cells (p less than .001), while the only tumor cells that lymphocytes from BCG-pretreated mice showed significant cytotoxicity against were S-91 target cells (p less than .01). Nonspecific cytotoxicity was not a factor in the effect of BCG-immune lymphocytes against S-91 target cells, since BCG-immune lymphocytes were not cytotoxic to Balb/C fibroblasts.