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Spergualin treatment-dependent delayed relapse of mouse T cell leukemia (DL812) after chemotherapy
Y Takeda1, T Kaneko, A Matsuzawa
1Department of Clinical Oncology, University of Tokyo.
Abstract:
A transplantable mouse T cell leukemia, DL 812, is characterized by high sensitivity to 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-chloroethyl)-1-nitrosourea hydrochloride (ACNU) and intensive systemic infiltration. When subcutaneously inoculated, DL812 cells invade many organs and cause marked splenomegaly without forming local tumors. Disseminated DL812 leukemias are clinically completely cured by a single intraperitoneal injection of 1 mg ACNU, but more ACNU-resistant leukemias relapse immediately. A novel antitumor antibiotic, spergualin, is effective against various mouse leukemias. The effects of its analog with stronger anti-leukemia activity, 15-deoxyspergualin (DSG), on the relapse of DL812 leukemias after ACNU treatment were investigated. DDD mice were subcutaneously inoculated with 10(6) DL812 cells and intraperitoneally injected with 1 mg ACNU once on day 11 and with 100 micrograms DSG daily from day 12 on. The relapses were clinically completely suppressed for at least 30 days. Winn assays with spleen cells revealed that host immunity did not play a major role in maintenance of the clinical cure. Thus, when DSG treatment was discontinued after 15 or 30 daily injections, leukemias relapsed immediately. When it was extended to 50 daily injections, permanent cure was attained in 1 of 15 mice but relapses occurred under DSG treatment in the others. DSG is available for combined treatment of the leukemia. The current and previous results suggest that DL812 leukemias may serve as a model in study on immunochemotherapy of the disease.
Insights
The study investigated 15-deoxyspergualin (DSG) to prevent relapse of ACNU-treated mouse leukemia. DSG suppressed leukemia relapse, but cure depended on treatment duration, suggesting its potential in combination immunochemotherapy.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- DL812 mouse T cell leukemia is sensitive to ACNU but prone to relapse.
- Spergualin and its analog 15-deoxyspergualin (DSG) show anti-leukemia activity.
- Investigating DSG's efficacy against ACNU-resistant leukemia relapse is crucial.
Purpose of the Study:
- To evaluate the effect of 15-deoxyspergualin (DSG) on preventing relapse of ACNU-treated DL812 mouse leukemia.
- To determine the role of host immunity in the maintenance of ACNU-induced cure.
- To explore DSG's potential as a combination therapy for leukemia.
Main Methods:
- DL812 leukemia cells were inoculated into DDD mice.
- Mice received ACNU followed by daily injections of DSG.
- Winn assays were performed to assess host immunity.
- Treatment duration and relapse rates were monitored.
Main Results:
- DSG treatment completely suppressed leukemia relapse for at least 30 days.
- Host immunity did not significantly contribute to the maintenance of cure.
- Relapses occurred upon discontinuation of DSG after 15 or 30 days.
- Permanent cure was achieved in 1 of 15 mice after 50 days of DSG treatment.
Conclusions:
- DSG shows promise in preventing leukemia relapse after ACNU treatment.
- Sustained DSG administration may be necessary for long-term remission.
- DL812 leukemia serves as a valuable model for immunochemotherapy studies.