Cancer stem cells targeted in malignant brain tumors

Immune system targets have been identified in cancer stem cells. These are the cells from which malignant brain tumors are believed to originate and regenerate. The researchers have also created an experimental vaccine to attack these targets.

Results of laboratory and animal studies were published in the online edition of Stem Cells Translational Medicine (2013; doi:10.5966/sctm.2013-0135). A phase 1 safety study in human volunteers with recurrent glioblastoma multiforme—the most common and aggressive brain tumor in adults—is underway. With standard care, which includes surgery, radiation treatment, and chemotherapy, median length of survival is 15 months for patients with glioblastoma multiforme.

Like normal stem cells, cancer stem cells have the ability to self-renew and generate new cells. In theory, if the cancer stem cells can be destroyed, a tumor may not be able to sustain itself, but if the cancer originators are not removed or destroyed, a tumor will continue to return despite the use of existing cancer-killing therapies.

The researchers identified certain fragments of a protein—CD133—that is found on cancer stem cells of some brain tumors and other cancers. In the laboratory, they cultured the proteins with dendritic cells, the immune system's most powerful antigen-presenting cells, which are responsible for helping the immune system recognize and attack invaders.

Studies in lab mice showed that the resulting vaccine was able to stimulate an immune response against the CD133 proteins without causing side effects such as an autoimmune reaction against normal cells or organs.

"CD133 is one of several proteins made at high levels in the cancer stem cells of glioblastoma multiforme. Because this protein appears to be associated with resistance of the cancer stem cells to treatment with radiation or chemotherapy or both, we see it as an ideal target for immunotherapy,” said senior author John Yu, MD, vice chair of the Department of Neurosurgery, director of surgical neuro-oncology, medical director of the Brain Tumor Center, and neurosurgical director of the Gamma Knife Program at Cedars-Sinai Medical Center in Los Angeles, California.

Yu added, “We have found at least two fragments of the protein that can be targeted to trigger an immune response to kill tumor cells. We don't know yet if the response would be strong enough to prevent a tumor from coming back, but we now have a human clinical trial underway to assess safety for further study."

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