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Clinical Trial Update: Brain Cancer Vaccine Doubles Patient Survival Time in Phase I Study

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Researchers from the Cedars-Sinai Medical Center reported their findings online Aug. 3 in Cancer Immunology, Immunotherapy.

The Phase I clinical trial included 16 newly diagnosed patients who could be properly evaluated between May 2007 and January 2010. At later follow-up, six patients (38 percent) — ranging from 49 to 66 months post-treatment — showed no evidence of tumor recurrence and were free of disease without current active treatment. Eight patients remained alive.

"Brain tumors evade the immune system to survive, and the vaccine is intended to alert the immune system to the existence of cancer cells and activate a tumor-killing response. We also are targeting cells that we believe generate and perpetuate cancers," said Keith L. Black, MD, who directs Cedars-Sinai's Cochran Brain Tumor Center, where the study was conducted, as well as its Maxine Dunitz Neurosurgical Institute, where the vaccine was researched and developed.

The vaccineis latest version, ICT-107, targets six antigens involved in the development of glioblastoma cells. The researchers also found evidence that the vaccine attacks some brain cancer stem cells, which some researchers consider the original source of tumor cells.

"The correlation of clinical responses to the level of antigen expression gives us confidence in our belief that a strong immunologic response is linked to clinical outcome. This finding supports our previous finding that immune responses are correlated to survival," commented John S. Yu, MD, the study's senior author.

Three of the tumor-associated antigens were found not only on brain tumor cells but also on brain cancer stem cells, and the researchers reported that a protein associated with cancer stem cells was decreased or eliminated from tumors of some vaccinated patients whose glioblastomas returned after treatment.

"Our findings suggest that targeting antigens that are highly expressed by cancer stem cells may be a viable strategy for treating patients who have glioblastoma," said Surasak Phuphanich, MD, director of the Neuro-Oncology Program at the Cochran Brain Tumor Center.

Cedars-Sinai's first dendritic cell vaccine began Phase I experimental treatments in May 1998. Dendritic cells are responsible for helping the immune system recognize invaders. They are derived from white blood cells taken from the patient in a routine blood draw. In the laboratory, the cells are cultured with synthetic peptides of the six antigens — essentially training the dendritic cells to recognize the tumor antigens as targets.

When the "new" dendritic cells in the vaccine are injected under the patient's skin in the armpit, they are intended to seek and destroy lingering tumor cells. Vaccine is administered three times at two-week intervals after standard radiation and chemotherapy.

With the ability of the latest version, ICT-107, to stimulate a targeted and controlled immune response established in this Phase I study, the vaccine moved into a Phase II multicenter, randomized, placebo-controlled trial in 2011.

Enrollment in the Phase II trial is expected to be completed in September.

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