Passive local anaphylaxis: demonstration of antitumor activity and complementation of intratumor BCG

Abstract

When an extracellular dye, Lissamine green, or 51Cr-labeled spleen cells were injected iv into C3H mice bearing small, partially necrotic 3-methylcholanthrene-induced transplantable fibrosarcomas (McC3), the tumor content of these circulating elements per unit weight was substantially lower than that of other selected organs. The level of these blood-borne materials was, however, significantly augmented by the intratumor induction of passive local anaphylaxis (PLA). The PLA-induced augmentation was inhibited by administration of the histamine and serotonin antagonist cyproheptadine; comparable increases were also induced by the intratumor injection of a histamine and serotonin mixture or BCG. The weekly intratumor induction of PLA in McC3 tumors resulted in the complete regression of a significant number of the tumors, and this therapeutic effect was eliminated by cyproheptadine treatment. The intratumor injection of BCG induced the regression of approximately 50% of injected tumors, and the combination of this immunostimulant treatment with the generation of PLA was more therapeutically effective than either treatment alone. PLA in the vicinity of solid tumors may, by increasing vascular permeability, potentiate antitumor effector mechanisms, particularly when these are BCG-stimulated. Despite this demonstration of a possible role of anaphylactic reactions in tumor immunity, no definitive evidence was found that active reagin-mediated local anaphylaxis occurred in C3H mice bearing the McC3 tumor, whether or not they were treated with immunostimulants.