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

Abstract

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). I n 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

Synergism between host anti‐tumor immunity and combined modality therapy against murine breast cancer

“…The observed therapeutic effect then would be interpreted as a reflection of complementary anti-tumor action between the effective dose of cytosine arabinoside and host cellular immunity which was not suppressed by that dose of the drug. The achievement of complementation in anti-tumor action between host immunity and chemotherapy also is suggested by the results of studies of cyclophosphamide therapy of a chemically-induced murine sarcoma (Moore and Williams, 1973), and of L-asparaginase therapy of the Gardner lymphosarcoma (Carter et al, 1973).…”

Control of a human tumour (ewing sarcoma) in mice by a single lethal dose of dimethyl‐myleran and bone marrow

“…Similarly, autulogous repopulation after lethal therapy may apply for a multitude of tumours without prohibitive metastatic bone marrow involvement. While the possibility of allogeneic repopulation must not be discarded, the additionally needed immunosuppression to ensure marrow engraftment after DMM may well affect adversely tumour control (Floersheim, 1969;Carter et al, 1973;Moore and Williams, 1973).…”

“…Experimentally, rats, mice, dogs and monkeys have been shown to survive lethal doses of DMM if they were subsequently restored with syngeneic or autologous bone marrow (Talbot and Elson, 1958;Floersheim and Elson, 1961;Kolb et al, 1974;Buckner et al, 1975;Floersheim and Storb, 1974). The fact that reconstitution with allogeneic marrow is only achieved after additional immunosuppression (Floersheim and Ruszkiewicz, 1969;Kolb et al, 1974), underlines the poor immunosuppressive activity of DMM, a feature which is likely to be advantageous for a cancer chemotherapeutic agent (Carter et al, 1973;Moore and Williams, 1973). The feasibility of cancer eradication with very large doses of DMM and syngeneic (Floersheim, 1969;Einstein et al, 1976) or autologous (Floersheim, 1981) haemopoietic reconstitution has been demonstrated with experimental tumours.…”

l-Asparaginyl-Trna Synthetase and l-Asparagine Synthetase Activities of l-Asparaginase-Sensitive and -Resistant Forms of the Mouse Gardner Lymphoma 6C3HED

“…The L-asparagine-sensitive tumour had been maintained by serial subcutaneous implantations in CBA mice at the Chester Beatty Research Institute, London (Carter, Connors, Weston & Davies, 1973). The L-asparaginase-resistant tumour was derived from solid L-asparaginase-sensitive tumour grown in mice, which were subsequently injected with L-asparaginase (Carter et al, 1973).…”

“…The L-asparaginase-resistant tumour was derived from solid L-asparaginase-sensitive tumour grown in mice, which were subsequently injected with L-asparaginase (Carter et al, 1973). It was further passaged in mice, injected intraperitoneally with L-asparaginase.…”