Eighty years of immunotherapy: a review of immunological methods used for the treatment of human cancer.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G A Currie.
Explore the source record for details and available documents.
In a microcytotoxicity assay the lymphocytes from cancer patients were tested on autologous and allogeneic tumour cells in vitro. In patients with a variety of tumours, extensive washing of the lymphocytes from those cases with advanced disease was found to greatly enhance their specific cytotoxic effects. This specificity was restricted to autologous tumour cells and allogeneic cells of similar histological origin. This cross-reacting cytotoxicity was not, however, universal, especially in cases of malignant melanoma. The cytotoxicity evoked by washing was abolished by the addition of the patient's serum. This serum effect showed a similar specificity to that found for lymphocyte cytolysis. The effect of washing, and the specific inhibitory effect of serum, was not detectable in early cases of primary malignant melanoma. The serum component responsible for inhibiting lymphocyte cytotoxicity had no detectable affinity for the target cells and appears to act on the lymphocyte surface, implying that tumour antigen may well be implicated.
Thymocytes from C57BL mice immunized with the DBA/2 lymphoma L5178Y exert in vitro an immunologically specific cytotoxic action against the target cells in the presence of bone-marrow cells. Neither the nonimmune bone marrow nor the immune thymocytes are by themselves cytotoxic. The cells in the bone marrow which take part in the cytotoxic action adhere to glass and are sensitive to anti-macrophage serum. These bone-marrow cells can also be rendered specifically cytotoxic by exposure to the supernatant obtained from a culture of immune thymocytes with the specific target cells. The thymocytes before they are confronted with the specific target cells are very radiosensitive; however, on coming into contact with the target cells, an immunologically specific increase in RNA synthesis occurs and thereafter the thymocytes' capacity to render bone-marrow cells cytotoxic is relatively radioresistant. Two classes of immune lymphocytes occur in mice immunized with allogeneic cells, those that are capable of killing target cells directly and those that produce a factor capable of rendering macrophages (or monocytes) specifically cytotoxic. In the thymus of immune animals only the latter are found while both categories are present in the spleen and lymph nodes of immune animals.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A microculture technique has been adapted to assay the cytotoxic properties of the lymphocytes from patients with malignant melanoma when cultured with their autologous tumour cells. In a series of patients with established melanoma specific autologous cytotoxicity was extremely uncommon, being detectable in only 3 out of the 22 cases studied. This cytotoxicity did not correlate with clinical staging of the disease but may well have been related to tumour volume. By autoimmunization of patients with an irradiated suspension of their own tumour cells the appearance of cytotoxic lymphocytes could be provoked in 5 out of the 12 patients studied. This cytotoxicity was detectable at the end of the first week after the autograft and disappeared by the third week. Cytotoxic lymphocytes did not correlate in any obvious way with the appearance of specific antitumour antibodies detected by immunofluorescence. So far there has been no evidence of a serum factor capable of blocking the lymphocyte cytotoxicity in these patients.The presence and possible significance of cytotoxic lymphocytes in patients with malignant disease is discussed.
Corynebacterium parvum used alone to enhance immunological reactivity produced transient inhibition of the growth of chemically induced isogenic mouse tumours. Attempts were made to combine C. Parvum with cyclophosphamide to see whether this would increase the latter's effectiveness in inhibiting early but established tumours. Of the various regimens tested, the administration of the C. parvum 12 days after a single dose of chemotherapy produced dramatic inhibition of tumour growth and resulted in complete and lasting regressions in up to 70% of tumour-bearing animals. The most important variable in this regimen is the time between the chemotherapy and the subsequent immunotherapy.It is possible that non-specific active immunotherapy with agents such as C. parvum may be a valuable adjunct to the conventional cyto-reductive treatments of cancer, but the time of administration of such therapy is probably critical for each tumour and for each chemotherapeutic regimen.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.