844 SUCCESSFUL TUMOR IMMUNOTHERAPY WITH CIMETIDINE BY AB-ROGATION OF SUPPRESSOR CELLS

Abstract

Immunotherapy has generally been aimed at stimulation of the patient's anti-tumor immune response. Since tumor growth may be associated with development of suppressor cells which could undermine an otherwise effective anti-tumor immune response, we have reasoned that an alternative immunotherapeutic strategy is the inactivation of suppressor cells by pharmacologic means, thereby allowing a more effective host anti-tumor immune response. Suppressor cells have a histamine H2 receptor on their surface which can be blocked by the H2 antagonist cimetidine (C). We therefore studied the effect of C on 3LL tumor in C57B1/6 mice. Tumors were allowed to grow until 7.5 mm at which time they were surgically removed, and mice were randomized to control or C groups. The latter received C in their drinking water at 0.2, 2.0 or 10.0 mg/ml. The mice receiving 10 mg/ml C had a significant decrease in metastatic development (25 and 54 surface pulmonary metastases in control mice at 5 and 12 days after surgery; 6 and 16 in the C group, p<.01). C at all three dosages produced a significant prolongation in survival (p<.01 for 0.2 and 2.0 mg/ml groups; p<.001 for 10.0 mg/ml C group). These effects were associated with suppressor cell inactivation (47% suppression in control; 21% in 10 mg/ml C group). We conclude that C slows metastatic development and prolongs survival by abrogation of suppressor cells. This suggests that a similar immunotherapeutic approach in human neoplasia is appropriate.