Antitumor Effect of Intratumoral Administration of Biological Response Modifiers: Induction of Immunosuppressive Acidic Protein, a Type of α1‐Acid Glycoprotein, in Mice

Abstract

The antitumor effects of biological response modifiers (BRMs) in an experimental mouse model, the “double grafted tumor system” were analyzed. Male BALB/c mice received simultaneous inoculations of Metn‐A fibrosarcoma cells on the right flank (106 cells) and left flank (2 × 105 cells) on day 0, and BRMs were injected intratumorally into the right tumor on days 3, 4 and 5. PSK (a protein‐bound polysaccharide preparation), interleuldn‐1 (IL‐1) and cepharanthin (R) 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 and tumor necrosis factor (TNF) cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) and IL‐6 inhibited neither the right nor the left tumor. Immunosuppressive acidic protein (IAP) in serum was increased transiently soon after intradermal injection of PSK, CR, OK‐432 and TNF in BALB/c mice. Lentinan, however, did not induce IAP. IAP in serum was gradually increased after intradermal inoculation of Meth‐A tumor in BALB/c mice. The biochemical difference between PSK‐induced IAP (early, inflammatory IAP) and Meth‐A‐induced IAP (late, tumor‐induced IAP) was investigated by crossed affinity immunoelectrophoresis with concanavalin A. IAP of murine serum was separated into 4 peaks. IAP in normal mouse was rich in high‐mannose type sugar chain (Peak 3) and contained no hybrid‐type sugar chain (Peak 4), which was present in inflammatory and tumor‐induced IAP. Inflammatory IAP was rich in biantennary sugar chain (Peak 2) and tumor‐induced IAP was rich in tri‐tetraantennary sugar chain (Peak 1).