Cyclophosphamide-induced tumour regression of cyclophosphamide-resistant L5178Y lymphoma through suppressor cells...

The series of experiments here described show that injection of cyclophosphamide (Cy) into mice bearing the L5178Y lymphoma caused partial or complete regression of this tumour. This effect was dependent on both the size of lymphoma and on the dose of drug administered. Cy-induced tumour regression was observed in mice in which L5178Y lymphoma had been implanted at least 10 days previously, and the dose required to cause neoplasm regression was found to be 100 mg/kg i.v., lower doses having no therapeutic effect. A key additional finding was that this same dose administered to lethally irradiated mice, or to T-cell-deficient mice bearing a 14-days neoplasm, failed to cause the L5178Y lymphoma regression. It was also demonstrated that this Cy-induced permanent or complete regression of L5178Y tumour is mediated by releasing memory antineoplasm effector cells from the inhibitory influence of suppressor Ly 1+ T cells. Tumour regression induced by Cy administration may be associated with elimination of Ly 1+ suppressor T lymphocytes, since the therapeutic effect of Cy was reversed by passive transfer of Ly 1+ T cells obtained from donor mice bearing a 14-days L5178Y lymphoma; thus, these results suggest that the therapeutic effect of Cy in this model is through its capability to preferentially eliminate Ly 1+ suppressor T lymphocytes, thereby permitting memory antitumour immune cells to generate a strong secondary immune response against this immunogenic lymphoma.