Mechanism of Action of Bria-IMT™ and Bria-OTS™
The mechanism of action of Bria-IMT™/Bria-OTS™ is currently under investigation.
We believe that Bria-IMT™/Bria-OTS™, activates the patient’s immune system to recognize tumor cells and destroy them. We hypothesize that Bria-IMT™/Bria-OTS™, exert their action by stimulating the antigen-presentation system (i.e. the system that presents antigen material on the surface of the tumor cells) – to be recognized by the T cells of the immune system. Specifically, Bria-IMT™/Bria-OTS™, may stimulate the dendritic cells, a key component of the antigen-presenting system, to display certain immunogenic (i.e., immune response-generating) protein fragments to T cells, which activates the T cells to destroy the tumor cells either directly, or by inducing antibodies to the tumor cells. In addition, we also have shown that Bria-IMT™ is capable of directly stimulating cancer-fighting T cells. This further boosts the immune response against the tumor cells and enhances anti-cancer activity.
Our preliminary analyses have shown several up-regulated genes in Bria-IMT™ that encode proteins known to be immunogenic (i.e. immune response-generating), suggesting that Bria-IMT™ can stimulate the immune system against the cancer cells.
Bria-IMT™ is a human breast cancer cell line which expresses Her2/neu (a protein well known for its overexpression in breast cancer but also present on other epithelial malignancies including ovarian, pancreatic, colon, bladder and prostate cancers). Bria-IMT™ has been engineered to produce and secrete granulocyte-macrophage-colony stimulating factor (GM-CSF), a protein that promotes dendritic cell function, a key component of the immune system, and hence activates the immune system.
Bria-IMT™ & Bria-OTS™
Potential Mechanisms of Specific Immune Activation in Advanced Breast Cancer
- Bria-IMT/OTS™ produces breast cancer antigens (proteins made by breast cancer cells).
- Bria-IMT/OTS™ secretes GM-CSF which further promotes dendritic cell-based antigen presentation (boosts the response).
- Breast cancer antigens are taken up by dendritic cells and “presented” to CD4+ and CD8+ T cells implicated in tumor destruction.
- Bria-IMT/OTS™ directly stimulates cancer fighting CD4+ and CD8+ T cells (further boosts the response).
- Bria-IMT/OTS™ efficacy depends in part on HLA matching of Bria-IMT/OTS™ and the patient.