The mycobacterium is an acid-fast, slow-growing bacillus. Most of its antigens are firmly attached to the cell wall. These have been classified into three groups: 1) antigens common to all mycobacteria, which can also be found in other bacteria such as Listeria, Corynebacterium and Nocardia spp.; 2) common antigens present on slow-growing bacteria; 3) species-specific antigens. Most studies on the soluble antigens have been based on vigorous experimental methods by which the cell wall was disrupted and solubilized. This crude antigen preparation was found to be a nonspecific stimulant of cell-mediated immunity, as well as a powerful adjuvant to vaccines used in experimental animals.
Repeated injection of Freund's complete adjuvant containing killed mycobacteria results in a response resembling autoimmune disorders (the so-called adjuvant arthritis in rats). BCG itself can induce nonspecific resistance to certain infections (or enhancement of others) and tumor growth suppression, attributed to various influences of the vaccine such as enhancement of macrophage cytotoxicity, increased production of natural killer cells, cytokines and cytotoxic T cells. Most of the above-mentioned properties are related to the high lipid content of the bac teria, up to 40% of its dry weight. These lipids include a variety of biologically active substances: trehalose 6,6'-dimycolate or 'cord factor', neutral red reactive sulfolipid, 6-O-methylglucose lipopoly-saccharide, phosphatides and waxes. A group of substances which have been studied extensively are the mycolic acids. (3-Mycolic acid is typical of BCG. It consists of three aliphatic chains of 11-28 carbons, linked by ester or hydroxyl residues to extensive hydrocarbon chains with a carboxyl side-chain at the link and at the end of the chain. A cyclopropyl group is present between the first two short chains. In the cell wall, these molecules are connected to sugars, containing arabinose and galactose, and with wax D. This complex is the molecule that gives the adjuvant activity. The nonspecific immune stimulation has been used in cancer management. Animal studies have demonstrated tumor regression following repeated local BCG infection. Viable BCG cells, injected into metastases of human malignant melanoma, led to marked tumor regression. Probably the most abundant use of BCG in cancer therapy is in bladder cancer. Intravesical administration is used for three purposes: 1) adjunctive therapy as a single treatment after complete tumor resolution to prevent tumor cell implantation and recurrence; 2) prophy-lactically, in repeated doses to prevent de novo recurrence of tumor following complete excision; 3) therapeutically, in repeated administrations to treat residual unresected tumor. Known adverse effects include regional adenitis, disseminated BCG infection and osteitis due to the BCG organism.
See also: Adjuvants; Mycobacteria, infection and immunity; Vaccines.
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