Mechanism of Action

The mechanism of action of Bria-IMT™ is currently under investigation.

We believe that Bria-IMT™, BriaCell’s lead product candidate, awakens the patient’s immune system to recognize tumor cells as foreign, and hence destroys them. We hypothesize that Bria-IMT™ 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, Bria-IMT™ 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 SV-BR-1-GM that encode proteins known to be immunogenic (i.e. immune response-generating).

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 associated 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.

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

In a clinical study, we observed a linear relationship between Bria-IMT™ exposure and the rising levels of CD40L (CD40 ligand) in a subject with a strong anti-tumor effect. 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 Bria-IMT™’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.

Publication – Frontiers in Immunology – May 2018arr

Poster Presentation – AACR – April 18, 2016arr

Bria-IMT™ Potential Mechanisms of Action for Breast Cancer

  1. Bria-IMT™ produces breast cancer antigens which are taken up by dendritic cells and “presented” to CD4+ and CD8+ T cells implicated in tumor destruction.
  2. Bria-IMT™ secretes GM-CSF which further promotes dendritic cell-based antigen presentation (boosts the response)
  3. Bria-IMT™ directly stimulates cancer fighting CD4+ and CD8+ T cells (unique to Bria-IMTTM)