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Treatment of Spontaneous Leukemia in AKR Mice with Chemotherapy, Immunotherapy, or Interferon¹

Department of Neoplastic Diseases, Mount Sinai School of Medicine and Hospital of the City University of New York, New York, New York 10029 [J. G. B., J. P.R., J. F. H.], and Litton Bionetics, Kensington, Maryland 20795 [E. Z.]

AKR mice are genetically destined to develop Gross (RNA) virus-induced lymphatic leukemia. Leukemic AKR mice treated with combination vincristine, cyclophosphamide (Cytoxan), and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea sustained a 180% increase of life-span. Combination chemotherapy plus immunization with neuraminidase-treated allogeneic (Gross virus-induced) G₂G leukemic cells intradermally resulted in 35% of animals surviving beyond 150 days without evidence of the disease. It is significant that allogeneic E₂G leukemie cells as immunogen were as effective in prolonging the life-span of the immunized leukemic AKR mice as were syngeneic leukemic thymocytes.

Virazole (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), an antiviral compound, alone showed no apparent antitumor effect. However, in experiments in which the clinically diagnosed leukemic AKR mice received a combination of cytoreductive therapy [vincristine plus prednisone or, more effectively, vincristine, Cytoxan plus 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, followed by Virazole], there was a noticeable reduction of the viral titer, a delay in the reappearance of viable clonogenic cells, and an increase in the survival time for the leukemic AKR mice as compared to those receiving cytoreductive therapy alone.

The effectiveness of purified mouse interferon in AKR mice was also examined. The decrease in the viral titer of animals that received interferon treatment was markedly greater than of those receiving a combination of cytoreductive therapy with Virazole or immunotherapy. The administration of mouse interferon had a direct effect on the appearance of the spontaneous leukemia in AKR mice. The median life-span of the control animals was 36 weeks, whereas 45% of the AKR mice treated with five doses of 5 x 10⁴ units of interferon are still alive at 54 weeks of age. Thus, interferon not only reduces the Gross murine leukemia virus titer in the chronically infected AKR mice but also significantly delays the appearance of the primary lymphoma.

¹ Presented at the symposium "Immunological Control of Virus-associated Tumors in Man: Prospects and Problems," April 7 to 9, 1975, Bethesda, Md. This work was supported by the National Cancer Institute Cancer Virus Program, Contract 1 CP 43225.

² Presenter.