Researchers Target Novel Vaccine for Approach for Brain Tumors

Study examines cellular and molecular mechanisms behind experimental vaccine.

Study examines cellular and molecular mechanisms behind experimental vaccine.

Researchers are working to develop a cancer vaccine that extends median survival in glioblastoma patients through the activation of the body’s immune system to fight the brain tumor.

In a study published online November 13, 2014 in the journal Cancer Immunology, Immunotherapy, researchers analyzed the cellular and molecular mechanisms behind the experimental vaccine, called antisense oligodeoxynucleootides (AS-ODN), in order to lay the ground work for future development and refinement.

"In recent years, researchers and the public have begun to realize the role that the immune system plays in both cancer prevention and treatment," said senior author Craig Hooper, PhD, in a press release. "The immune system has great potential for helping fight cancer. This study helps give us a roadmap for future brain cancer vaccines."

Following a phase 1 trial in 2001 that saw tumor shrinkage in 8 out of 12 patients tested, a second phase 1 trial was held for AS-ODN, which consists of portions from the patient's own tumor. The tumor samples are removed during surgery, treated with a drug overnight, and packaged inside a diffusion chamber to be inserted into the abdomen, which offers easy access to immune cells.

AS-ODN knocks down IGF-R1, a receptor that is vital for tumor growth and metastasis, in order to cause the tumor cell to self-destruct.

During the initial trial, researchers believed molecules from the self-destructing tumor were released through pores in dime-sized chambers to activate the immune system, at which point the immune cells travel to the brain and kill the remaining tumor cells not removed by surgery.

"But no one had really examined the material coming out of the chambers to find out what was activating the immune response," Dr. Hooper said.

Prior research shows that exosomes, a form of cell-based antigen, are small enough to pass through the chamber's pores.

Lab test results show that exosomes are released from the chambers in a continual stream that provides a consistent source for immune-cell activation. Additionally, when mouse model brain tumors were given the harvested exosomes, the growth of the tumors was slowed.

The trial also included a test of the vaccine on a new group of 12 patients with recurrent glioblastoma, of which 6 of the patients exhibited immune responses to therapy.

"The best predictor of a positive clinical outcome from the vaccine was an intact immune system," Dr. Hooper noted.

The next phase of clinical trials, which is expected to begin in January 2015, will treat patients immediately following their first brain surgery for tumor removal, prior to chemotherapy. Researchers also hope to strengthen the immune response to the vaccine, which will make it more effective.

"We expect these patients will stand to benefit most from the treatment," Dr. Hooper added.