Phase I/II Study of a Toll-like Receptor Agonist as an Adjuvant to Tumor Associated Antigents (TAA) Mixed with Montanide ISA-51 VG for Patients with Recurrent Central Nervous System Tumors

Sharon Gardner, M.D.

New York University School of Medicine

Funded in September, 2011: $200000 for 3 years
LAY SUMMARY .

LAY SUMMARY

back to top

Can a broadly targeted vaccine effectively prevent brain tumor recurrence in patients?

Clinical researchers will determine whether an experimental vaccine can successfully stimulate the immune system in patients following treatment for brain tumor to prevent its recurrence.

            Conventional malignant brain tumor (glioma) therapy, consisting of surgical removal, followed by radiation and chemotherapy, rarely lengthens a patient’s life for more than two years. While these treatments help kill cancerous cells composing the brain tumor mass, individual cancer cells that have already infiltrated brain tissue in many other brain areas live on and eventually produce widespread tumor recurrence in the brain. Evidence indicates that a patient’s innate immune cells, called dendritic cells, initially recognize a tumor’s “antigens” (peptides) that are found on the cancer cells’ surface. But, the cancer cells send out signals that silence the dendritic cells before they can summon “adaptive” immune cells that have been taught to recognize and kill those specific antigens. Scientists, therefore, have been exploring the use of experimental vaccines, made from a patient’s cancer cells, to stimulate the patient’s immune system to more forcefully attack the tumor. The NYU investigators examined tissues from a large number of surgically removed brain tumors and identified several peptides that constitute the majority of antigens found on tumor cells. They then developed a vaccine composed of a combination of these peptides, and hypothesize that this vaccine will stimulate a strong immune response in patients with recurrent glioma, resulting in their improved survival.

            They will study the vaccine’s effects, and monitor any possible side effects, first in nine patients and thereafter in a total of 36 patients. Each patient will receive an MRI scan of the brain tumor prior to starting vaccine treatment. Then, the vaccine will be administered to each patient every three weeks. Patients will again receive an MRI scan a month following the third vaccination, and every three months thereafter. Investigators will assess patients’ immune responses through blood samples taken prior to vaccine treatment and one week following each successive vaccination. They will evaluate whether patients develop a specific immunologic response to the target peptides. This response will be reflected by an increased number of adaptive immune T cells that target the specific type of antigens that are contained in the vaccine. Patients will be considered treatment responders if these specific immune T cell types increase from undetectable levels prior to vaccination to detectable levels following vaccination.  They will correlate the MRI scans of each patient’s tumor with the patient’s immune T cell levels to derive initial indications of the vaccine’s effectiveness in treating the tumor and preventing recurrence.

            Significance: This vaccine approach, if successful, would represent a major advance in treating deadly brain tumor and improving and extending patient survival. Moreover, the approach could be adapted to treating other types of cancers as well.