Efficacy of intralesional BCG therapy in guinea pigs with disseminated tumor.

It has been previously demonstrated that transplanted syngeneic tumors established in the skin of inbred (strain-2) guinea pigs regressed and regional lymph node metastases were eliminated after intralesional injection of viable Mycobacterium bovis (BCG). During the course of this reaction there is the development of tumor-specific immunity. This experimental model was further manipulated in order that it would more closely approximate a clinical reality. In the present study an evaluation was made of the effectiveness of the developing tumor-specific immunity in this BCG therapy model, to abrogate artifically induced distant tumor deposits and to assess the requirement for tumor-specific immunity in the local BCG-mediated tumor regression. During BCG-mediated regression of established intradermal tumor, the developing tumor-specific immunity inhibited the growth of artificially induced vascular metastases in animals receiving a 10(4) or 10(5) tumor cell dose. However, there is a direct causal relationship between the distant tumor burden and the escape of skin tumor and regional lymph node metastases from BCG-mediated regression. Thus, multiple tumor deposits as low as 10(4) cells are capable of competing for or preempting tumor-specific immune reactivity, which must be a requirement during some phase of the intralesional BCG-mediated therapy of established tumor and regional lymph node metastases. Thus, a significant therapeutic effect could be achieved in guinea pigs with established skin tumors and limited vascular metastases when the modality of therapy included BCG intralesional injection, followed 6 weeks later by surgery of the treated skin tumor and regional lymph node.