Involvement of cytotoxic T-lymphocytes in the antitumor activity of spergualin against L1210 cells.

Spergualin exhibited a strong antitumor effect against L1210(IMC), a tumor cell line which has been maintained in BALB/c X DBA/2 F1 (hereafter called CD2F1) mice in the Institute of Microbial Chemistry. Mice inoculated i.p. with 10(5) cells of L1210(IMC) survived more than 60 days by daily i.p. administration of spergualin for 9 days at 5 mg/kg/day, which was started 1 day after the tumor inoculation. These cured mice rejected a second inoculation of 10(6) cells of L1210(IMC), but they did not reject the inoculation of 10(2) P388 cells. In Winn's tumor neutralization assay and in the 51Cr release assay, the T-cell fraction prepared from the spleens of the cured mice had higher cytotoxic activity against L1210(IMC) than whole spleen cells. The cytotoxic activity of spleen cells was diminished by treatment with anti-Thy-1.2 or anti-Lyt-2.1 antibody and complement. Therefore, the effector cells involved in the immunological rejection should be regarded as cytotoxic T-lymphocytes. The cytotoxic activity of these T-lymphocytes was measured during and after the spergualin administration for 9 days, and high activity was observed from 1 day after the final spergualin administration. The antitumor effect of spergualin against L1210(IMC) was much lower in T-cell-deficient athymic mice. These results suggest that cytotoxic T-lymphocytes are involved in the antitumor action of spergualin against L1210(IMC) in vivo.