Mechanism of Action

The mechanism of action of BriaVaxTM is currently under investigation.

We believe that BriaVaxTM, a cancer vaccine, awakens the patient’s immune system to recognize tumor cells as foreign, and hence destroys them. We hypothesize that BriaVaxTM exerts its action via changing the tumor’s antigen-presentation system {i.e. the system that presents antigen material on the surface of the tumor cell – to be recognized by the T cells of the immune system as either self (i.e., safe) or foreign (i.e., to be destroyed)}. Specifically, BriaVaxTM 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 a humoral (antibody-generating) response.

Our preliminary analyses have shown several up-regulated genes in BriaVaxTM that encode proteins known to be immunogenic (i.e. immune response-generating).

BriaVaxTM is a Her2/neu (a protein well known for its overexpression in breast cancer but also associated other epithelial malignancies including ovarian, pancreatic, colon, bladder and prostate cancers) positive human breast cancer cell line we engineered to produce and secrete granulocyte/macrophage-colony stimulating factor (GM-CSF), a protein that promotes dendritic cell function. We hypothesize that particularly strong tumor-directed clinical responses might occur if BriaVaxTM peptides (protein fragments) were displayed on the surface of dendritic cells and the same peptides were produced by the patients’ cancer cells.

Our research has provided us with the valuable insights with respect to the process of presenting BriaVaxTM peptides on the surface of dendritic cells. Besides unraveling BriaVaxTM’s mechanism of action, these findings provide our scientists with the necessary information to design additional vaccines for multiple cancer indications.

In a clinical study, we observed a linear relationship between BriaVaxTM exposure and the rising levels of CD40L (CD40 ligand) in a subject with a strong anti-tumor effect (please see the publication in the Clinical Trial section). CD40L is a protein that is expressed on components of the immune system including activated T cells, B cells, platelets, monocytic cells, natural killer (NK) cells, mast cells, and basophils. CD40L is known as one of the strongest stimulants of the immune system resulting in dendritic cell maturation, and rising serum levels of CD4+, CD8+, and NK cells, i.e., immune cells known for their anti-tumor activities. Additionally, the CD40/CD40L pathway is critical for the development of protective anti-tumor activity by providing a key initial step in the development of humoral (B cell/antibody-mediated) immunity. However, CD40L has also shown immune-suppressive activity in some tumor models. By higher expression of CD40/CD40L levels, tumors have been able to avoid both T cell and antigen-presenting cell (APC) compartments, and to establish an immunosuppressive tumor microenvironment.

Taken together, while details on BriaVaxTM’s mechanism of action have already begun to become apparent, our upcoming phase I/IIa study is expected to provide a framework for the testing of our current model.

 

Poster Presentation – AACR – April 18, 2016arr