Biological Properties of Non-Toxic Water-Soluble Immunoadjuvants from Mycobacterial Cells

The use of mycobacteria in cancer therapy, either as systemic or as local immunoadjuvants, has been proposed [9, 11, 16]. These microorganisms can enhance the resistance of the host to a variety of attacks (bacterial, protozoal, viral or tumoral) by nonspecific mechanisms. Because they are powerful immunoadjuvants, they can also potentiate specifically the immune response to a given antigen. This capacity may be particularly valuable in the case of neoantigens that are weak immunogens. In recent years, both approaches have been used clinically and experimentally [11, 13, 20]. BCG (Mycobacterium tuberculosis, bacillus Calmette-Guerin), Hemophilus pertussis and Corynebacterium parvum are amongst the most popular candidates for clinical and animal experimentation in this field. H. pertussis and more recently C. parvum have been shown to increase the susceptibility of mice to histamine [3, 14] and may therefore expose the host to a wide variety of allergic and physiological accidents. Although BCG lacks this histamine-sensitizing activity, it is still capable of inducing many of the noxious effects observed after the injection of H. pertussis or C. parvum. Thus, killed BCG administered in saline sensitizes to tuberculin, produces lymphoid hyperplasia and increases the reactivity of mice to endotoxins [8, 18]. The decreased resistance towards lipopolysaccharides may be the cause of a great number of pathophysiological disturbances. Mycobacteria administered as a water-in-oil emulsion also produce allergic polyarthritis in the rat, a response which has been considered to indicate autoimmune disease [17]. Several investigators have suggested that insoluble Wax D extracted from virulent strains was the immunoadjuvant component of mycobacterial cells and that this substance is also responsible for allergic polyarthritis [17, 19].