A Vaccine for the Most Prevalent Glioblastoma Subtype

Title: A Vaccine for the Most Prevalent Glioblastoma Subtype
Investigators: Duane Mitchell and John Sampson
Grantee: Duke University

Even though every patient’s brain tumor is different, the tumors of roughly a third of all patients with glioblastoma share a particular mutation in the EGFR gene.  EGFR normally helps to maintain the checks and balances in brain cells, and the mutated version (called EGFRvIII) is bad news.  EGFRvIII disrupts normal cell safeguards, thereby allowing cancer cells to grow out of control, invade into the brain, seed new tumors, and resist radiation treatment and chemotherapy.  Finding effective therapies for this most prevalent and aggressive type of glioblastoma is thus an urgent goal.

Immunotherapy may help to reach this goal by harnessing the power of the human immune system to fight cancer.  Just like a flu vaccine stimulates the immune system to attack the flu virus, an EGFRvIII vaccine would turn the body’s natural defenses against EGFRvIII—and thus against these aggressive tumors.  Even better, because EGFRvIII only exists in tumor cells and not in healthy brain cells, it is a perfect target for immune system-based therapy.

With this in mind, Drs. John Sampson and Duane Mitchell embarked on a project early last decade at Duke University to develop a vaccine targeting EGFRvIII.  ABC2 partnered with several organizations to drive the initial stages of this exciting project forward.  With the help of funding from ABC2, Drs. Sampson and Mitchell developed an EGFRvIII vaccine and matured its safety, efficacy, and method of delivery ahead of human clinical trial testing.

Building from this early work, the EGFRvIII vaccine has achieved remarkable signs of success in the clinic.  It has proven safe and effective in three separate Phase 2 clinical trials for glioblastoma, each of which saw patients’ lives extended beyond what is typical for the EGFRvIII patient population.  In the majority of patients treated with the vaccine, the vaccine did exactly what it was designed to do—that is, kill cancer cells that carry EGFRvIII.

The EGFRvIII vaccine is continuing clinical testing in glioblastoma.  Several additional Phase 2 trials are ongoing, and planning for a larger-scale, Phase 3 clinical trial is underway.  If these trials are successful, this vaccine could change the treatment landscape for the many patients with this EGFR mutation in their brain tumors.