STUDIES ON IMMUNOLOGICAL EFFECTS OF BCG AND ITS COMPONENTS - THEORETICAL AND THERAPEUTIC IMPLICATIONS

Abstract

BCG has had significant antitumor effects in rodents and man. In mice, BCG is capable of increasing lymphocyte mediated immunity to allogenic leukemia cells and creating pseudoimmune cytotoxic lymphocytes when administered alone. Lymphocyte activating factor (LAF) produced by macrophages, a T-[thymus-derived]-lymphocyte mitogenic substance, is increased significantly by the administration of BCG and may play a role in the evocation of cytotoxic cells. BCG acts as a mitogen for splenic and T cells in vitro. Macrophages were important regulators in the response, since a critical concentration (at least 0.25-0.5%) were required for T cell stimulation and a high concentration (.apprx. 5-10%) inhibited splenic lymphocytes. LAF was increased 20-fold above baseline in vitro by BCG. Methanol extraction residue (MER) stimulated T and splenic cells as did whole BCG. A delipidated cell fraction (DMC) stimulated only splenic non-T lymphocytes. BCG antagonized several sorts of immunosuppression and may be useful clinically in this regard. There is also the possibility of antagonizing the myelosuppressive toxic effects of chemotherapeutic agents through the stimulation of the macrophage made granulocyte colony stimulating factor. If BCG can induce cytotoxic lymphocytes (or macrophages) in vitro, it may be possible to use these in clinical adoptive immunotherapy. BCG is a useful prototype of an immunological adjuvant with antitumor activity. Elucidation of its actions on lymphoid cells and its effects in therapeutic situations can serve as a model for future investigations of other substances with similar potential.