Treatment of a mouse lymphoma by L‐asparaginase: Success depends on the host's immune response

Regression of the L‐asparaginase‐sensitive Gardner lymphosarcoma was investigated in normal CBA mice and in CBA mice deficient in thymus‐processed lymphocytes (T cells). In normal animals, solid subcutaneous grafts of the tumour disappeared completely following one intraperitoneal injection of L‐asparaginase (50 IU) given 10 days after tumour inoculation. The local tumour was impalpable after 3 or 4 days and there was early and massive destruction of the graft though surviving tumour cells persisted in the vicinity of blood vessels for up to 24 h after treatment. These cells subsequently disappeared and there was an intense local inflammatory response dominated by macrophages. In mice deficient in T cells, the Gardner lymphosarcoma initially regressed as in the normal group but the small perivascular accumulations of surviving tumour cells did not disappear; they persisted and all the animals eventually died with local and disseminated lymphosarcoma 22–24 days later. Their recurrent tumours were invariably asparaginase‐resistant. These results indicate that, although the main effect of L‐asparaginase is the biochemical destruction of sensitive tumour cells, residual asparaginase‐resistant cells are normally destroyed by the host's immune response. In T‐cell‐deficient mice, the immune component does not operate effectively and asparaginase‐resistant tumour cells grow back and kill the animals. T cells appear to be involved in the immune response to the Gardner lymphosarcoma and some possible modes of action of T cells are discussed.