Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most malignant and deadly form of cancer of the central nervous system in humans. Death results from the rapid, aggressive, and infiltrative growth of GBM cells in the brain.

Glioblastoma multiforme (GBM) tumors are highly invasive and usually spread rapidly. These tumors contain glioma stem-like cells which are highly resistant to therapy and lead to high rates of tumor recurrence. GBM patients have a median survival of about 15 months after diagnosis.

Current treatments are limited to reducing symptoms and prolonging a deteriorating quality of life. Consequently, new therapies and treatments are urgently needed.

The standard of care for GBM consists of maximum safe surgical resection – complete surgical removal is virtually impossible due to the anatomy of the tumor – followed by radiotherapy with concomitant chemotherapy with temozolomide (TMZ). Most gliomas recur even after treatment; TMZ increases median survival by only about 2 – 3 months compared with surgery and radiotherapy alone.

GBM represents about 23% of all primary brain tumors. In the United States and the European Union, GBM has been designated as a rare disease allowing Orphan Drug Designation to be granted to drugs intended to treat GBM.

CRxIMT

CRxIMT is a potential anti-tumor immunotherapy combining cannabinoids for the treatment of Glioblastoma Multiforme.

Cardiol intends to pursue a combination therapeutic strategy focusing on orphan indications in oncology, initially GBM, involving the use of immunologically-based therapies combined with cannabinoids. Cardiol has recently filed a provisional patent application for a combination of cannabinoids with immunotherapy. Research collaborations are under active discussion with centers of excellence in North America to develop a unique technology platform for the development and delivery of new cancer therapies to the pharmaceutical market.

Cardiol’s patent-pending cancer therapeutic platform envisages the use of certain immune modulators to stimulate cells of the immune system to target tumors. Tumor cell killing can ultimately be achieved in the body by activated white blood cells, such as tumor-infiltrating lymphocytes (TILs) and lymphokine-activated killer (LAK) cells; however, many tumors have an immunosuppressive environment to shield the tumor from the patient’s immune system. Cardiol anticipates that cannabinoids may modify this immunosuppressive ‘shield’.

The cannabinoids CBD and THC have both been shown pre-clinically in in vivo and in vitro models to have potentially beneficial effects in GBM. These studies have shown that cannabinoids have anti-tumor activity and could be of utility in the treatment of GBM. Cannabinoids have been shown not only to reduce GBM tumor growth via inhibition of tumor cell proliferation and angiogenesis (reducing blood flow and availability of nutrients and oxygen to the tumor), but also to induce tumor cell death by apoptosis as a consequence of increasing reactive oxygen species (ROS) levels. Cannabinoids were further shown to inhibit the invasiveness and stem cell-like characteristics of GBM tumors. In an early clinical study, a combination of cannabinoids has been shown to significantly increase one-year survival rates in GBM patients.

Cardiol believes that cannabinoids may represent one way of modifying the tumor environment to enable tumor cell killing. Thus, an immunotherapeutic approach combined with cannabinoids, each acting via different pathways, may be complementary and offer the potential for a synergistic effect in the treatment of GBM.