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Production of Antitumor T-Cells in Tumor-bearing Mice Treated with Tumor Vaccine and 6-Mercaptopurine¹

Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo 170, Japan

Treatment with both L1210 murine leukemia cell vaccine (L1210 vaccine) and 6-mercaptopurine (6-MP) induced antitumor effector cells in the spleen and peritoneal cavity of L1210-bearing mice. The in vivo neutralization test showed that the spleen cells and peritoneal cells of mice treated with both agents, but not with either agent alone, prolonged the life span of animals simultaneously inoculated i.p. with live L1210 cells. These results indicate that these antitumor cells were associated with the augmented therapeutic response in L1210-bearing mice treated with both agents.

The neutralizing activity of peritoneal cells was located to a fraction not adhering to plastic flasks and abolished by the treatment of anti-Thy 1.2 antibody and complement, indicating that they were T-cells. The in vitro antiproliferation test confirmed these observations. The spleen cells and peritoneal T-cells of these mice suppressed L1210 proliferation. Their activity was tumor specific since they suppressed the in vitro proliferation of L1210 but not P388 and L5178Y cells. The in vivo association of antitumor T-cells with the augmented therapeutic effect was substantiated by the finding that rabbit anti-mouse thymocyte globulin abolished the induced therapeutic effect.

¹ This research was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare (56-4); by the Ministry of Education, Science and Culture, Japan; and also by the Princess Takamatsu Cancer Research Foundation. This is Paper 19 of a series on murine leukemia vaccine.

² Recipient of the Award of the Society for the Promotion of Cancer Research, Japan. To whom all correspondence should be addressed.

Received 2/19/82. Revised 3/25/85. Accepted 3/26/85.