Adjuvant-antigen requirements for active specific immunotherapy of microscopic metastases remaining after surgery.

We studied the conditions required for eradication by immunization of occult lymph node metastases which remained after surgical removal of an intradermally transplanted cavian hepatoma. Guinea pigs that received no postsurgical treatment all died with progressively growing lymph node metastases. The growth of these metastases could be prevented in a significant proportion of the animals by postsurgical treatment with vaccines containing oil-in-water emulsions of Mycobacterium bovis strain Bacillus Calmette-Guérin (BCG) cell walls admixed with live or irradiated tumor cells. Vaccines containing living tumor cells cured most of the guinea pigs but produced tumors at the vaccine sites in a few animals. Irradiated tumor cell vaccines were not tumorigenic but required more tumor cells for successful therapy. Therapy was dependent both on the dose of tumor cells and on that of BCG cell walls. Microgram doses of BCG cell walls were required for a therapeutic effect; milligram doses of BCG cell walls inhibited the therapeutic response. Animals rendered tumor free by postsurgical vaccine therapy rejected an intradermal challenge with living tumor cells.