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Researchers Examine CMV Antigens in Novel Glioblastoma Immunotherapies

By November 11, 2015Glioblastoma ("GBM")

Glioblastoma (“GBM”) is the most common and aggressive malignant primary brain tumor in humans, accounting for approximately 12% to 15% of brain and nervous system cancers. GBM progresses rapidly and is unusually deadly – on average, only 3% of GBM patients survive five years beyond their initial diagnosis.

Currently, GBM treatment depends on multiple factors including the patient’s age, overall health, and the location of the tumor in the brain. The standard of care is surgical debulking followed by radiation and chemotherapy. Even with this invasive and aggressive course of therapy, median survival is less than 16 months. Median survival without treatment is less than five months. Given these poor patient outcomes, new and effective treatments for glioblastoma are desired.

Targeted immunotherapy may provide a promising adjunct or alternative to conventional GBM treatment. Immunotherapy is a fundamentally different way of treating cancer that “teaches” or “retrains” the immune system to attack tumors. While conventional therapies are non-specific and may damage surrounding normal tissues, a targeted immunotherapy may offer a highly specific and potentially long-lasting treatment approach.

Developing a broadly applicable GBM immunotherapy requires the identification of antigens (antigens are used to steer or direct the immune response) that are consistently expressed on tumor cells. In recent years, investigators have found that as many as 90% of malignant gliomas are infected with cytomegalovirus (“CMV”) and that multiple CMV gene products are expressed in these tumors. As evidence mounts, CMV antigens are being examined as a key potential component of GBM immunotherapies.

A 2014 study led by Dr. Smita Nair, Ph.D., a Duke University researcher, took a first step in demonstrating the possible utility of CMV-directed immunotherapy in vitro. Dr. Nair’s approach, described as antigen-specific vaccination, is designed to induce an immune response against CMV pp65, an antigen commonly expressed in GBM tumors.

In Dr. Nair’s study, T cells from patients with GBM were stimulated with autologous dendritic cells (dendritic cells are among the most effective antigen presenting cells) stimulated with CMV pp65 RNA. The CMV-specific T cells recognized and killed GBM tumor cells obtained from the same patient, indicating sufficient levels of CMV pp65 antigen expression for recognition by the immune system and T cell-mediated killing.

Building on this approach, Duke University researchers combined this CMV-directed immunotherapy with a tetanus booster vaccine believed to stimulate the immune system. In March of this year, researchers published data that showed the potential utility of their treatment approach in humans with GBM. Patients who received the immunotherapy, alongside standard of care treatment, lived 26 months on average, a promising outcome in this hard to treat cancer.

While the research is still in its early stages, it may support the rationale for developing a CMV-targeted immunotherapy in patients with GBM. In October, VBI announced that it had applied its eVLP Platform in the development of a novel therapeutic vaccine candidate for GBM. VBI’s approach may allow for the efficient delivery of multiple CMV antigens and could be capable of mobilizing a broad and robust anti-tumor immune response.

To learn more about VBI’s GBM immunotherapy candidate, visit: http://www.vbivaccines.com/gbm/

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