Novel Cancer Vaccine Approach For Brain Tumors

Novel Cancer Vaccine Approach For Brain Tumors
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Glioblastoma is the most common aggressive primary brain tumor, and despite advances in standard treatment, the median survival is about 15 months (compared to 4 months without treatment). Researchers have been working on a cancer vaccine that would extend that survival by activating the patient's immune system to fight the brain tumor. A study published online November 13th in the journal Cancer Immunology, Immunotherapy drilled down to the cellular and molecular mechanisms behind the vaccine, paving the way for further development and refinement of this new experimental treatment.
The study reports on the results of a second phase 1 clinical trial, after the first phase 1 trial in 2001 saw tumor shrinkage in eight out of 12 patients tested. The vaccine consisted of portions of the patient's own tumor. Specifically, samples of the patients' tumor were removed during surgery, treated overnight with a drug, and packaged inside a diffusion chamber which was then inserted into the abdomen providing immune cells easy access. The drug in this therapy - antisense oligodeoxynucleootides (AS-ODN) - knocks down IGF-R1, a receptor shown to drive tumor growth and metastasis. Research had shown that blocking this receptor with agents like AS-ODN could cause the tumor cell to self-destruct.
In the original trial, the researchers thought that the molecules from the patient's self-destructing tumor were released through pores in the dime-sized chambers and activating the immune system. Once activated in the abdomen, the immune cells would travel to the brain where they would kill the remaining tumor cells that were not removed by surgery.
The researchers have previously done research on antigen presentation. One form of cell-based antigen are exosomes, small membrane-bound particles that bud off of cells and can activate the immune system. Because exosomes are small enough to pass through the chamber's pores, the researchers tested for their presence in the material that seeped out of the sheaths in the lab. They showed that not only were exosomes present, but that they were released from the chambers in a slow and continual stream, providing an ongoing source for immune-cell activation. The researchers also showed that when exosomes were harvested and given to mouse models of brain tumor, the exosomes alone slowed tumor growth.
Finally, the researchers showed that the AS-ODN molecules used to kill cancer cells also activated the immune system.
The vaccine was also tested on a new group of 12 patients with recurrent glioblastoma. In this round, six of the 12 patients tested had immune responses to therapy. The patients who did not respond, may have been immune-compromised from chemotherapy.
In the next phase of clinical trials expected to open in January of 2015, the researchers plan to treat patients immediately after their first brain surgery for tumor removal, before chemotherapy is given.