Regression of polyoma tumor metastasis by combined unblocking and BCG treatment--correlation with induced alterations in tumor immunity status.

Abstract

AbstractImmunotherapy, in the form of inoculations of “unblocking” antitumor sera alone or combined with BCG and splenectomy, was tried in a metastasis model in animals. W/Fu rats were exposed to progressively growing polyoma tumor isografts which were subsequently excised, and then rechallenged with an isograft of the same tumor as a “metastasis”. The immunological manipulation was initiated at the time of rechallenge and, although it was not capable of preventing tumor outgrowth, it caused a complete regression of the outgrowing tumor nodules within a few weeks in 7/7 and 5/16 rats in two different experiments. An attempt was also made to inhibit well‐established spontaneous tumor metastasis to the lung by repeated inoculations of unblocking antitumor serum. Prolonged survival was obtained in four out of nine rats and one of these animals was free of tumor when killed after 4 months. The spread of the tumor to various organs was significantly restricted by the therapy, indicating partially inhibited tumor growth. An attempt was made to establish correlations between inhibition of tumor growth in vivo and certain alterations in the antitumor immunity as analyzed by in vitro techniques. Disappearance of serum blocking activity and appearance of rat complement‐dependent cytotoxicity in serum was seen in all rats with regressing tumors but not in the other animals, although they had received the same treatment. The lymphocyte cytotoxicity was increased to about the same extent in regressor and progressor rats.