The researchers also found evidence that the vaccine attacks some brain cancer stem cells, considered the original source of tumor cells. These self-renewing cells appear to enable tumors to resist radiation and chemotherapy and even regenerate after treatment. Cancer stem cells are especially appealing targets: killing the stem cells is believed to improve the chances of destroying a tumor and preventing its recurrence.
"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, vice chair of the Department of Neurosurgery, director of the Brain Tumor Center, professor of neurosurgery and senior author of the article.
Three of the tumor-associated antigens (HER2/neu, TRP-2 and AIM-2) are found not only on brain tumor cells but also on brain cancer stem cells, and the researchers reported that a protein (CD133) associated with cancer stem cells was decreased or eliminated from tumors of some vaccinated patients whose glioblastomas returned after treatment.
"Previous studies showed an increase in CD133 expression in patients who underwent treatment with radiation and chemotherapy. 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 and professor of neurology with Cedars-Sinai's Department of Neurosurgery and Department of Neurology.
Phuphanich and Christopher J. Wheeler, PhD, principal investigat
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Cedars-Sinai Medical Center