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6-Mercaptopurine-induced Potentiation of Active Immunotherapy in L1210-bearing Mice Treated with Concanavalin A-bound Leukemia Cell Vaccine¹

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

While the combination of L1210 murine leukemia cell vaccine (L1210 vaccine) with 6-mercaptopurine (6-MP) or 6-thioguanine produces a therapeutic response greater than that induced by either of these agents alone, its combination with cyclophosphamide, N⁴-behenoyl-1-ß-D-arabinofuranosylcytosine, or 5-fluorouracil does not produce such a response. The administration of cyclophosphamide, N⁴-behenoyl-1-ß-D-arabinofuranosylcytosine, or 5-fluorouracil alone resulted in a response as great as, or greater than, that induced by 6-MP alone. This and the finding that the 6-MP-induced response was more pronounced upon its delayed rather than its early administration indicate that 6-MP-induced reduction of the tumor burden does not explain this augmentation.

The combination of 6-MP and L1210 vaccine was not effective in mice bearing 6-MP-resistant L1210 leukemia; however, an augmented response occurred when the tumor burden was reduced by N⁴-behenoyl-1-ß-D-arabinofuranosylcytosine, indicating that reduction of the tumor burden by 6-MP was only partially associated with augmentation of the therapeutic response.

Augmentation was associated with vaccine-induced antitumor immunity because it was induced by the combination of 6-MP and concanavalin A-bound, but not concanavalin A-free L1210 vaccine. This augmentation was dependent on the timing of the L1210 vaccine administration. The combination was not effective in mice bearing P388 leukemia, indicating the tumor specificity of the augmentation. These results shown that 6-MP not only reduced the tumor burden but also potentiated the vaccine-dependent antitumor immunity, resulting in the induction of an augmented therapeutic response.

¹ This research was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare (56-4) and the Ministry of Educatin, Science and Culture, Japan, and also by Biomedical Science, Tokyo. This is Paper 16 of a series on murine leukemia vaccine.

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

Received 3/ 1/82. Accepted 10/26/83.