[Differences of antitumor effect of various BRMs by intratumoral administration]

The antitumor effects of biological response modifiers (BRM) in a new experimental mouse model, the "double grafted tumor system", were analysed. BALB/c mice received simultaneous inoculations of Meth-A fibrosarcoma cells on right flank (10(6) cells) and left flank (2 x 10(5) cells) on day 0, and BRMs were injected intratumorally into right tumor on day 3, 4 and 5. The growth of the left-flank tumor was the real target for the evaluation of a given drug after 21 days. PSK (a protein-bound polysaccharide preparation), IL-1 and Cepharanthin cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) inhibited neither the right nor the left tumor. Spleen cells from PSK-treated tumor bearing mice produced macrophage chemotactic factor (MCF) after 48 hrs cultivation in the presence of Con A or Meth-A tumor cells. MCF producing cells were indicated to be L3T4 positive cells. On the other hand, PMN activated by PSK treatment produced MCF in the culture supernatant. Therefore, our present and previous studies on the antitumor effect of BRM in the double grafted tumor system show that intratumoral administration of BRM first induces neurophils in the right tumor via an IL-8-like factor and then cytotoxic macrophages are induced by MCF. Then Lyt-1 (L3T4)-positive cells are induced in the right regional lymph nodes and in the spleen, probably via IL-1, which might be produced from macrophages in contact with tumor cells. Subsequently, Lyt-1-positive cells reach the left tumor through the blood stream, come into contact with Meth-A tumors and then produce MCF. Intratumoral administration of PSK in the right tumor thus induces cytotoxic macrophages in the left, non-treated tumor, thereby bringing about the regression of the distant tumor.