AUGMENTATION OF SPECIFIC CELL-MEDIATED IMMUNE-RESPONSES TO TUMOR-CELLS IN TUMOR-BEARING RATS PRETREATED WITH THE ANTI-LEUKEMIA DRUG BUSULFAN

  • 1 January 1981
    • journal article
    • research article
    • Vol. 66  (4) , 659-665
Abstract
Lethal growth of a syngeneic transplanted tumor ([rat fibrosarcoma]KMT-17 cells) was inhibited in inbred WKA rats pretreated with the antileukemia drug busulfan (BU). The lethal growth of KMT-17 was not inhibited by pretreatment with cyclophosphamide, adriamycin or ftorafur. With the Winn assay, spleen cells from BU-pretreated KMT-17-bearing rats (TBR) inhibited the growth of admixed KMT-17 cells more strongly than did spleen cells from BU-untreated TBR. The augmented tumor inhibitory activity of spleen cells was KMT-17-specific; this activity was abrogated by in vitro treatment of spleen cells with anti-T [cell] serum and guinea pig complement. Augmentation of the immune response to KMT-17-associated antigen(s) in BU-pretreated TBR was also demonstrated in lymphocyte-mediated cytotoxicity; it was detected by a 51Cr release assay and by a delayed-type hypersensitivity with a radioisotope footpad assay. Tumor regression in BU-pretreated rats was demonstrated to be mediated by the augmentation of T cell-mediated immune responses to tumor-associated antigens. The tumor inhibitory effect of BU was abrogated by adoptive transfer with thymus cells from normal rats, but not with those from BU-pretreated rats 1 day before tumor inoculation. The augmentation of the antitumor immune responses by pretreatment with BU may be because BU selectively inhibited the suppressor cells or their precursors.