Innovative Brain Tumor Vaccine Offers New Hope
In Vivo Vaccination With Tumor Cell Lysate Plus CpG Oligodeoxynucleotides Eradicates Murine Gliobastoma. Anhua Wu, Seunguk Oh, Soheila Gharagozlou, Raji N. Vedi, Katya Ericson, Walter C. Low, Wei Chen, and John R. Ohlfest. Journal of Immunotherapy. 30(8):789-797, November/December 2007.
1. What were important findings of the study?
Dr. Ohlfest’s research team has shown the effectiveness of a cancer vaccine containing tumor cell extract plus an immune stimulator in curing glioblastoma (a type of brain tumor) in mice. The vaccine increased the number and activity level of special types of immune cells (dendritic cells, T cells) in the lymph nodes of the mice; the vaccine also increased the number of special immune cells (tumor-reactive lymphocytes) capable of directly killing glioblastoma cells. One type of immune cell (CD4+ T lymphocyte) was found to be especially important in destroying the tumors. Most important, the vaccine was able to eradicate or significantly reduce the tumors in the mice. Judged by survival time and imaging, 55% were called tumor-free.
2. How are the study findings important for improving treatment of glioblastoma multiforme (a lethal type of human brain tumor)?
Brain tumors are among the most lethal of human cancers in children and adults. The study may help develop improved treatments for glioblastoma multiforme, a type of human brain tumor that is typically fatal. Currently, even though 90-99% of the tumor can be surgically removed, the remaining tumor cells will cause the tumor to redevelop. In addition to the current treatments of surgery, radiation and chemotherapy, doctors need more potent, cost-effective immune-based therapies that can be widely used to increase survival times of patients with glioblastoma. New therapies also need to be less toxic to patients than current ones. Current immune therapies involve purifying and culturing very large numbers of immune cells in the laboratory before they are combined with inactivated tumor protein and then administered to patients. The process is very costly and time-consuming and requires high levels of technical expertise, making it very challenging to use in hospitals. As a result, such immune therapies are not widely available. A potent and cost-effective direct vaccine not requiring time-consuming culture of the patient’s own immune cells would allow more glioblastoma patients to be treated with immune therapy. Although the researchers used a specialized tumor cell line (GL261) in this study, they suggest that tumor cells from any patient undergoing surgery could be used to create a personalized vaccine, thereby eliminating the need for any tissue culture and enabling most brain tumor patients to receive a vaccine within several days after surgical removal of as much of the tumor as possible.
3. What are some weaknesses and limitations of the study?
Because of genetic or other differences between animals and humans, a vaccine developed in an animal model may produce different and unexpected results when used in humans. The study’s 55% cure rate in mice using the tumor cell lysate/CpG vaccine is very promising. However, the tumor cell lysate (extract) used in the vaccine was made from special GL261 tumor cells occurring in mice. The GL261 cells are known to cause a considerably stronger immune response than do cells from glioblastomas occurring naturally in humans. For that reason, vaccines made with patients’ own tumor cells may prove to be less potent.
4. In summary, why is this study important to patients with brain cancer?
This is the first study to show that personalized brain tumor vaccines can be made without culturing and growing the patient’s own immune cells in the laboratory. New direct vaccines would be much simpler and more-cost effective than current immune therapies and could be offered to the almost any patient who undergoes surgery. The goal of using the vaccine would be to stimulate the immune system to prevent recurrence of the disease. Although the Ohlfest study focused on glioblastoma, the results may be applicable to direct vaccines for other types of brain tumors, and even to cancers outside of the brain.
5. What are the next steps?
A clinical trial of the tumor cell lysate/CpG ODN vaccine in patients with glioblastoma is needed.