Engineered Probiotic Candida albicans for Immunotherapy
This invention comprises genetically modified Candida albicans strains engineered to express and secrete heterologous cytokines or chemokines. These engineered strains function as localized delivery vehicles to augment host immunity and prevent or treat infections like candidiasis.
Description
The core technology utilizes recombinant nucleic acid constructs integrated into the C. albicans genome. These constructs feature a constitutive TDH3 promoter to drive continuous expression and a SAP5 signal sequence to ensure the protein is successfully secreted out of the fungal cell. The strains are designed to deliver specific immune-signaling molecules, such as IL-17A, CXCL1, CXCL2, or CXCL5 directly to mucosal surfaces. By secreting these factors, the engineered yeast can bypass natural immune deficiencies. For instance, in individuals with T-cell defects who cannot produce sufficient IL-17A, these "probiotic" yeast strains provide the necessary signals to trigger protective neutrophil responses and reduce the pathogenicity of the fungus itself.Applications
- Probiotic Therapeutics: Development of oral or topical probiotics to prevent candidiasis in high-risk populations.- Immunocompromised Care: Treatments specifically tailored for HIV patients or those on immunosuppressive therapies who are prone to fungal infections.
- Mucosal Vaccines: Utilizing engineered strains to induce protective immunity against secondary fungal or bacterial exposures.
- Autoimmune Support: Potential use as a localized alternative to systemic biologic therapies that often carry high infection risks.
Advantages
- Targeted Delivery: Enables localized secretion of therapeutic proteins directly at common infection sites like the oral cavity or GI tract.- Bypasses Immune Deficiencies: Restores protective signaling in immunocompromised subjects who lack natural T-cell function.
- Reduced Pathogenicity: Genetically modified strains exhibit lower virulence and kidney burden compared to wild-type strains in vivo.
- Constitutive Activity: Uses a permanent, non-regulated promoter to ensure a steady supply of the therapeutic protein.
- Probiotic Competitive Edge: Engineered strains can outcompete more harmful wild-type strains at mucosal surfaces while inducing a protective immune response.