The findings detailed in an upcoming peer-reviewed paper provide a rationale for the encouraging clinical results observed with Bria-IMT™, an immunotherapy from BriaCell Therapeutics, in current and past clinical testing. The paper will appear in Frontiers in Immunology, the 5th most cited journal in Immunology worldwide. Bria-IMT™, also known as SV-BR-1-GM, has caused remarkable reduction of tumor size in some patients with advanced metastatic breast cancer. Understanding Bria‑IMT™’s mechanism of action is extremely important, not only for developing further clinical refinements; it may shed light on basic immune mechanisms important in many other areas. BriaCell is currently enrolling patients in a Phase IIa trial (NCT03066947) with Bria-IMT™ and a rollover trial (NCT03328026) with Bria-IMT™ alone or in combination with other immunotherapies.
The peer-reviewed paper provides evidence for the unique immune-enhancing activity of Bria-IMT™, which is believed to set the Bria-IMT™ approach apart from all other similar therapies. Bria-IMT™ contains a number of factors, in particular HLA-Class II molecules, i.e., specific markers that distinguish the body’s own cells from cells recognized by the body as foreign. These factors directly activate CD4+ “Helper” T cells, a key component of the immune system, which may produce a vigorous attack on tumor cells resulting in clinical tumor regressions (i.e., reduction in the tumor size). In patients with advanced breast cancer who have failed other therapies, complete or even partial regressions are difficult to achieve. BriaCell has previously reported such responses in patients with advanced metastatic breast cancer, not only in soft tissue and visceral areas, but even within the brain, responses which have not been typically seen in similar trials. BriaCell has devoted significant resources to further advance its clinical and preclinical studies.
“We are very pleased with the acceptance of our paper in this prestigious peer-reviewed immunology journal”, stated Dr. Williams, BriaCell’s President & CEO. “Our investigations into the mechanism of action of Bria-IMT™, addressed in the paper, support our hypothesis that direct activation of T cells by Bria-IMT™ is an important factor that contributes to the substantial tumor shrinkage we have seen in patients in whom HLA‑Class II molecules match with Bria-IMT™.
According to the American Cancer Society, about 41,400 patients are expected to die of breast cancer in the US in 2018. With the support of our investors, we have been capitalizing on the observations in this paper to develop a novel off-the-shelf personalized immunotherapy, Bria-OTS™, which will allow us to match over 90% of the patients with advanced breast cancer. Our goal is to combat this deadly disease and improve patient outcomes”.
“These findings provide a scientific rationale for why patients with an HLA-Class II version also present in Bria-IMT™ have achieved objective clinical benefits from the Bria-IMT™ regimen”, stated Dr. Markus Lacher, BriaCell’s Head of R&D and the lead author of the paper. “They also build the foundation for our strategy to develop Bria-OTS™, our off-the-shelf personalized immunotherapy for advanced breast cancer patients. We look forward to seeing more data in the coming months as we develop Bria-OTS™ as a new approach to treating breast cancer. We are grateful to our collaborators for their cooperation and expert advice”.
The details of the upcoming publication are the following:
Journal: Frontiers in Immunology
Section: Cancer Immunity and Immunotherapy.
Article type: Original Research Title: SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes
The abstract of the manuscript can be accessed via the following link: https://www.frontiersin.org/articles/10.3389/fimmu.2018.00776/abstract
BriaCell is an immuno-oncology focused biotechnology company developing a targeted and safe approach to the management of cancer. Immunotherapy has come to the forefront in the fight against cancer, harnessing the body’s own immune system in recognizing and selectively destroying cancer cells while sparing normal ones. Immunotherapy, in addition to generally being more targeted and less toxic than commonly used types of chemotherapy, is also thought to be a potent approach with the potential to prevent cancer recurrence.
Bria-IMT™ (SV-BR-1-GM), the Company’s lead product candidate, is derived from a specific breast cancer cell line. It is genetically engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), a substance that activates the immune system. We believe that Bria-IMT™ helps the body to recognize and kill tumor cells by activating T cells that attack the tumor and B cells that produce anti-tumor antibodies.
The results of two previous proof-of-concept clinical trials (one with the precursor cell line not genetically engineered to produce GM-CSF and one with Bria-IMT™) produced encouraging results in patients with advanced breast cancer. Most notably, one patient with metastatic breast cancer responded to Bria-IMT™ with substantial reduction in tumor burden including breast, lung, soft tissue and brain metastases. BriaCell is currently conducting a Phase I/IIa clinical trial for Bria-IMT™ in patients with advanced breast cancer. In this trial, Bria-IMT™ treatment appeared safe with similar instances of tumor reduction as those observed in the earlier proof-of-concept trials. This trial is listed in ClinicalTrials.gov as NCT03066947. The trial is being conducted along with the co-development of BriaDX™, the Company’s companion diagnostic test. Additionally, the FDA recently approved the roll-over combination study of Bria-IMT™ with pembrolizumab [Keytruda®; manufactured by Merck & Co., Inc.] or ipilimumab [Yervoy®; manufactured by Bristol-Myers Squibb Company] for patients previously treated with Bria-IMT™ in the Company’s ongoing Phase I/IIa clinical trial in advanced breast cancer. The roll-over trial is listed in ClinicalTrials.gov as NCT03328026.
BriaCell is also developing Bria-OTS™, an off-the-shelf personalized Immunotherapy. Bria-OTS™ is a set of cell lines similar to Bria-IMT™ which are being engineered to express pre-manufactured HLA alleles. With a combined total of 15 different alleles Bria-OTS™ is expected to be able to match more than 90% of the US population. BriaCell’s BriaDX™ companion diagnostic reveals patient HLA types. One or two Bria-OTS™ cell lines carrying matching alleles are planned to be administered per patient. Bria-OTS™ eliminates the complex manufacturing logistics required for other personalized immunotherapies and is regarded as a personalized therapy without the need for personalized manufacturing.
Yet another item in the BriaCell pipeline is a novel, selective protein kinase C delta (PKCδ) inhibitor. PKCδ inhibitors have shown activity in a number of pre-clinical models of RAS genes’ transformed cancers including breast, pancreatic, non-small cell lung cancer and neuroendocrine tumors (such as carcinoid tumors).
For additional information on BriaCell, please visit our website: http://briacell.com.