Immunotherapy with BCG: approaches to human malignant melanoma based on a guinea pig model

Attempts to treat guinea pigs with advanced melanoma involved reducing the tumor burden by excision of the cutaneous tumor and treating residual metastatic disease (lymph node) with BCG. All efforts to treat guinea pigs with lymph node metastases by injection of BCG into sites other than the cutaneous tumor failed. A successful combination treatment was surgical excision of the cutaneous tumor 1 to 7 days after intralesional injection of BCG. In some experiments the number of BCG reaching the superficial distal axillary node was determined. Injection of BCG into the cutaneous tumor, footpad and flank led to the accumulation of about the same number of bacteria in the superficial distant axillary node The number of BCG in the superficial distant axillary (SDA) node following intranodal injection was 10 times greater than the number of BCG in the SDA node following injection of the cutaneous tumor. The failure of footpad, flank, and intranodal routes of BCG infection suggests that the number of BCG reaching the superficial distal axillary node is not the factor determining success or failure. All experiments point to the conclusion that infection of the cutaneous tumor is a prerequisite for eradication of regional lymph node metastases. Injection of BCG into a cutaneous tumor may be the most effective method of inducing antitumor immunity and antimycobacterial immunity. Immunity against tumor antigens and mycobacteria may both be critical in eliminating lymph node metastases.