Influence of L-asparaginase on antibody production and growth of tumors in allogeneic mice.

SUMMARY The effect of L-asparaginase on imm'unosuppression in mice was studied with procedures measuring the ability to produce circulating antibodies against sheep erythrocytes and allogeneic tumor cells and the'incidence of tumor take in the allogeneic mice. The production of anti-sheep erythocyte antibodies on primary immune response in C57BL/Na X A/Jax F1 mice was markedly suppressed at a dose of 25 i.u. of L-asparaginase/mouse, and the degree of the immunosupression was just parallel to the dose of enzyme administered. On the contrary, the enzyme failed to suppress the secondary immune response to sheep erythrocytes. The production of cytotoxic antibody in mice bearing allogeneic tumors was also depressed by the enzyme treatment; however, the duration of the immunosuppression was temporary. Successful tumor allograft was observed with enzyme treatment in the systems of CS7BL/Na versus L12l0 and CBA/Na versus EL4. The minimum effective dose for allogeneic tumor take was 1000 i.u. of L-asparaginase/mouse for a system of CS7BL/Na versus L1210 and 200 i.u. for a system of CBA/Na versus EL4. Tumor allograft in a system of CS7BL/Na versus 6C3HED-OG or-RG was regressed at a dose of 800 to 1000 i.u. of L-asparaginase. Histological fmdings revealed that the cells associated with immune reactions were scarce in the tumor-grafted area and ascites of the enzyme-treated mice, as compared to those of the 0.9% NaCl solution-treated mice. These results indicate that L-asparaginase acts as one of the potent immunosuppressive agents. The mechanisms of immunosuppression by the enzyme are discussed.