Treatment of normal BALB/c mice i.p. with a number of adjuvants, including
pyran copolymer, the copolymer of polyinosinic and
polycytidylic acids, Bacillus Calmette-Guérin,
glucan, and
dextran sulfate, rendered macrophages nonspecifically
cytostatic for syngeneic
tumor cells. Macrophage activation was highly 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. Moreover, 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, and
thymosin, were ineffective in prolonging the life of
tumor-bearing mice.
Pyran treatment i.p. was the most effective antitumor adjuvant in two separate
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.