Immunosuppression by L-Asparaginase

Abstract

IN 1953 Kidd¹ discovered that the growth of certain murine lymphomas is inhibited by the administration of guinea-pig serum. Broome² found the suppressive factor to be L-asparaginase, an enzyme widely distributed in nature but present in serum only in guinea-pigs and in rodents of the superfamily Cavioidea³. Tumours affected by L-asparaginase are unable to synthesize L-asparagine, an amino-acid considered non-essential for normal tissues^4–6. The neoplasms, it is thought, are killed when their stores of L-asparagine are depleted by the action of L-asparaginase. The discovery of L-asparaginase-resistant variants of sensitive tumours that have sufficient L-asparagine synthetase to free them of dependence on exogenous L-asparagine supports this idea⁷. Because normal cells have been considered independent of exogenous L-asparagine, and thus resistant to the enzyme, a tumour-specific killing effect is possible with L-asparaginase. Indeed, dramatic results have been observed follow ing treatment with L-asparaginase of mice with established leukaemia⁸ and dogs with advanced lymphosarcoma⁹. Clinical trials with the enzyme are now proceeding^10,11. The work to be described here shows that, in addition to its anti-tumour effects, L-asparaginase is immunosuppressive in the mouse.