Antitumor activity of tritiated tumor polysaccharide substance (H3-TPS) in sarcoma 180 of mice.

Small doses of H3-TPS given to newborn mice have been found to induce protection in 70% of mice transplanted with sarcoma (Sa) 180. Mice rendered tolerant with large doses of TPS and DNA from Sa 180 in early life developed large tumors after transplantation with Sa 180. Subsequent treatment with H3-TPS gave rise to 90% cure, the result of "reverse tolerance" (Makari JG: Nature 205:1178, 1965). Macrophages (M phi s) selectively phagocytose polysaccharides and are thus labeled by H3-TPS. Radioisotope studies showed that the greater the tritium level in a tumor, the smaller its size, with the highest levels found at the cured tumor area (CTA). The radioactivity in progressively deeper samples of tumors demonstrated a bimodal peak in activity in large tumors, indicating inability of most M phi s to pierce the tumor, and a peak in small tumors indicating penetration of tumor by M phi s. Mice whose M phi s have already been stimulated by microbial infection have much higher cure rates and much higher H3-TPS uptake at the CTA. The local increase of uptake of H3-TPS at the CTA in the immunostimulated groups (whether by experimental stimulation or by natural infection) is believed to reflect increased proliferation and increased phagocytosis leading to M phi stimulation and tumoricidal activity. In the "reverse tolerant" group, in which the uptake of H3-TPS is low despite a high ratio of of H3-TPS uptake in CTA/tumor, the mechanism of cure seems to be one of marked stimulation by H3-TPS of the M phi surface membrane without phagocytosis, resulting in the activation of M phi s to tumoricidal activity. Thus M phi stimulation and M phi activation seem to be the basis for the antitumor effect of H3-TPS.