BCG w/MK-2206
Candidate Overview
Parental BCG efficacy is mainly hampered by its low induction of apoptosis along with high secretion of the immunosuppressive cytokine IL-10. We found that the host transcription factor FOXO3 mediates both, BCG-induced apoptosis and inhibition of IL-10 secretion. The novel vaccination procedure consists of induction of FOXO3 activity, during BCG vaccination, using an anti-cancer drug, the AKt inhibitor MK-2206.
Sponsor / Lead Developer: Institut Pasteur de Tunis (IPT)
Development partner(s): Translational Health Science and Technology Institute (THSTI)
Primary Indication: Prevention of Mtb infection or sustained infection
Other Indication(s): Prevention of TB disease
Target Population(s): Adolescents, Adults, Children, Infants, and To be determined
Target Route of Administration: Intradermal
Immune tissue localization: Lung and Lymph node
Immunological responses: Other and T-cell
Preclinical Animal Models: Guinea pig and Mouse
Intended to elicit trained immunity: Yes
Additional Immunologic Response Information
HYPOTHESIZED | DEMONSTRATED |
|
| Immune Response | Macrophages | T-cell |
| T-cell phenotype | CD4 CD8 Effector and Central Memory T Cells |
|
| T-cell functional profile | Polycytotoxicity Mycobacterial growth inhibition | IFN-γ TNF-α IL-17 |
| Preferential immune tissue localization | Lung Lymph node |
|
| Trained immunity | Yes |
Related Publications
- Co-Administration of Anticancer Candidate MK-2206 Enhances the Efficacy of BCG Vaccine Against Mycobacterium tuberculosis in Mice and Guinea Pigs. (Front. Immunol., 2021)
- FOXO3 Transcription Factor Regulates IL-10 Expression in Mycobacteria-Infected Macrophages, Tuning Their Polarization and the Subsequent Adaptive Immune Response. (Front Immunol., 2019)
- Forkhead box O3 (FOXO3) transcription factor mediates apoptosis in BCG-infected macrophages. (Cell Microbiol., 2014)
Additional Information
Animals (mice and guinea pigs) were vaccinated with the parental BCG. Twenty four hours later, MK-2206 was administrated at the same site of BCG vaccination (intradermal). Animals receiving MK-2206 were more protected than the ones receiving BCG alone.