CHAIN is focused on the development of orally delivered anti-infective and anti-cancer vaccines.
Our proprietary Clostridium butyricum platform strain is non-pathogenic and is based on a well-known probiotic strain that has been used extensively in Asia with proven safety and efficacy.
CADD platform strain spores can be engineered to produce specific immunogenic and antigenic proteins and peptides that are well suited for delivery to the colon, where they have been shown to induce significant T-cell and humoral responses in murine models. Additionally, the CADD platform strain produces naturally expressed metabolites that play a key role in gut and immune homeostasis.
Therapeutic proteins and peptides can be engineered using CHAIN’s extensive, patent-protected genetic manipulation methods to express in a variety of intracellular and extracellular locations.
Immune Checkpoint Inhibitors (ICI’s) are proving to be a new class of effective anti-cancer agents, however it has been observed that some patients exhibit tumour resistance to ICI’s, suggesting a need for the development of new combination therapies to overcome this issue.
Recent clinical studies suggest that C. butyricum probiotic strains can enhance the efficacy of existing ICI’s for a variety of cancer types. Stimulation of the mucosal immune response can be achieved with orally delivered CADD spores, which germinate to the lower GI tract and have been shown to induce antigen specific T-cell and humoral immune responses.
These improvements to ICI treatments can potentially be further amplified by the expression of tumour-specific oncological antigens or proteins to specifically induce an antigen-specific immune response which may further enhance ICI therapeutic modality.
CHAIN is currently developing and testing a number of therapeutic candidates which we believe have the potential to enhance the activity of current ICI’s, by modulating the host immune response.
CHAIN’s anti-infectives programme has developed antigenic peptides for oral vaccination against a number of pathogens including Human Rotavirus (HRV), Human Papilloma Virus (HPV) and SARS-CoV-2.
Our collaboration with the University of Oxford aims to develop a superior oral vaccine for HRV that is highly thermostable, with the goal of subverting vaccine inequality in low-income countries. The candidates for this collaboration have been developed by CHAIN and are currently in pre-clinical testing at the University of Oxford. Pre-clinical testing will utilize both healthy and malnutrition-induced enteropathy murine models to assess and refine a new live, bacterial spore based anti-HRV vaccine to address the efficacy issues of existing vaccines in low-income populations, where disease of the small intestine commonly results in immune dysregulation.
Oral vaccine candidates using the CADD platform aim to bypass the small intestine and deliver directly to the colon, which has been shown to remain healthy and intact in cases of enteropathy, while also exploiting the anti-inflammatory metabolites that are naturally produced.
The CADD platform offers a clearly differentiated vaccine approach, where the potential of its novel delivery capability combined with the oral administration of a stable, spore-based product (designed to induce a specific anti-HRV immune response) is projected to overcome the current vaccine issues and be more effective in malnourished populations.