ASSOCIATION OF MACROPHAGE ACTIVATION WITH ANTITUMOR ACTIVITY BY SYNTHETIC AND BIOLOGICAL AGENTS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (9) , 3338-3343
Abstract
Treatment of normal BALB/c mice i.p. with a number of adjuvants, including pyran copolymer, the copolymer of polyinosinic and polycytidylic acids, BCG, glucan and dextran sulfate, rendered macrophages nonspecifically cytostatic for syngeneic tumor cells. Macrophage activation was dose dependent. The validity of the inhibition of DNA synthesis assay for measuring macrophage induced cytostasis of target cells was proven by demonstrating a concurrent decrease in RNA synthesis and a reduction in viable tumor cell number. Conditioned supernatants from pyran activated macrophages did not significantly decrease [3H]thymidine incorporation by freshly added leukemia cells. Biological or synthetic agents that activated macrophages were generally effective systemic antitumor agents against the M109 lung carcinoma. Drugs that did not activate macrophages, such as typhoid vaccine, tilorone, levamisole, WY-13876 [3-(p-chlorophenyl)-2,3-dihydro-3-hydroxythiazolo[3-2-a]benzimidazole-2-acetic acid] and thymosin, were ineffective in prolonging the life of tumor-bearing mice. Pyran treatment i.p. was the most effective antitumor adjuvant in 2 tumor models, and suppression of tumor growth appeared to be related not only to an increase in macrophage tumoricidal function, but also to a larger influx of macrophages responding at the tumor site.

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