Specific immunotherapy of established visceral micrometastases by BCG-tumor cell vaccine alone or as an adjunct to surgery

Abstract

A vaccine of Bacillus Calmette-Guérin (BCG) admixed with tumor cells induced systemic immunity and had a therapeutic effect on subclinical, disseminated micrometastases. Inbred strain 2 guinea pigs given intravenous injections of either 10(4), 10(5) or 10(6) syngeneic L10 hepatocarcinoma cells were vaccinated after metastatic foci were established in the lung parenchyma. The studies demonstrate that under defined conditions of vaccine preparation and regimen, nontumorigenic preparations of BCG and tumor cells can cure the majority of animals of otherwise lethal visceral metastases. Histopathologically it was determined that immunization with these vaccines prevented the progressive growth of pulmonary micrometastatic foci approximately 0.1 mm in diameter. However, in this micrometastasis therapy model, the number of metastatic tumor foci is a major limitation in the efficacy of vaccine therapy. No protection against L10 tumor was achieved when antigenically distinct but syngeneic L1 hepatocarcinoma was used in the vaccine, suggesting that this is a tumor-specific immunotherapeutic procedure. This BCG-L10 tumor vaccine was also effective in curing guinea pigs of minimal disseminated tumor burden when administered after surgery of an established skin tumor and draining lymph node.