Immunoadjuvant effects of Candida albicans and its cell wall fractions in a mouse lymphoma model

Chemical, ultrastructural, and immunoadjuvant properties of Candida albicans (CA) and of a number of its fractions have been characterized through the analysis of the antitumor activity of soluble and insoluble cell wall components. CD2F₁ mice were inoculated IP with Moloney virus-induced lymphoma LSTRA and treated with bis-1-chloroethyl-nitrosurea (BCNU) on day +5 after tumor challenge. A significant increase of the antitumor efficacy of BCNU treatment was found in mice inoculated with CA as immunoadjuvant on days -14 and +1 (-14/+1 schedule) with respect to tumor challenge. However, no significant difference in survival time was found between mice treated with BCNU alone and those treated with BCNU plus either soluble mannan or glucan-protein fractions extracted from CA and administered according to -14/+1 or -7/+1 schedules. On the other hand, mice treated with BCNU plus the insoluble glucan fraction (wall 'ghosts') given on days -14/+1 or even on day -7 only (i.e., without boosting after tumor challenge) survived longer than animals treated with BCNU alone. The immunoadjuvant effect of CA and of other 'classic' immunoadjuvants, such as BCG and Corynebacterium parvum, was completely abolished by total-body irradiation (400 R) given 5 h before the first administration of the agent on day -7 prior to tumor challenge. These results indicate that: (a) the minimal structure required for the expression of the immunoadjuvant effect of CA is the insoluble, β-glucan component of the cell wall; (b) the soluble components of CA cell wall (i.e., mannan and glucan-protein) per se do not show any detectable immunoadjuvant effect in the present animal-tumor system; they may, however, 'modulate' this effect, as shown by the fact that whole CA, but not the insoluble β-glucan, needs a boosting injection for the expression of its immunoadjuvant properties; (c) the immunoadjuvanticity of CA is radiosensitive.