Does the immune system hold clues to the spontaneous regression of some cancerous tumors?
“Ignore him and he’ll go way,” is common advice when dealing with a pest in your life, but does the same hold true for cancer? Researchers in Norway seem to think so, at least in some cases of invasive breast cancer.
Two groups of women were followed over consecutive 6-year periods. One group underwent regular mammography screenings; the other did not. For every 100,000 women routinely screened in a 6-year period, 1,909 received a diagnosis of invasive breast cancer, compared with 1,564 women who did not get regular screenings.
Before jumping to conclusions, Bianca Santomasso, MD, PhD, a post-doctoral associate at Rockefeller University in New York City, offered a caveat about the study: “[Researchers] never actually showed a tumor disappearing.” She said that while the notion that any cancer can just disappear is “very intriguing,” it is difficult to prove.
“It’s an invisible phenomenon,” Dr. Santomasso said. “I could have had cancer last week, and if my body fought it off or eliminated it, we wouldn’t know I had cancer last week.”
Immune Cells Become Tumor Assasins
Ongoing research indicates that the body’s immune system plays a pivotal role in the fight against cancer. Dr. Santomasso has been working with Robert Darnell, a Howard Hughes Medical Institute investigator and head of Rockefeller’s Laboratory of Molecular Neuro-oncology, to examine the impact of paraneoplastic cerebellar degeneration (PCD) on cancer. PCD is a rare neurodegenerative disease triggered when immune cells known as CD8+ cytotoxic T cells detect the cdr2 protein expressed in tumors and attack cdr2-producing cells in an attempt to protect the body from the cancer. They rampage out of control, infiltrating the brain and killing neurons that also express the cdr2 antigen.
Dr. Santomasso described the immune system’s attack on the neurons as “devastating for PCD” but explained that it is an important mechanism in the fight against cancer. “It’s keeping their tumors at bay,” she said. Dr. Santomasso and Dr. Darnell are attempting to separate the tumor-fighting properties of this process from its destructive behavior against the neurons in the brain. “Is it possible to take the lesson from this and develop a tumor vaccine or some type of therapy?” she wondered.
To investigate this, Dr. Santomasso and her colleagues injected healthy mice with the cdr2 protein. Next, they isolated the genes in the potent cdr2-specific CD8+ cytotoxic T cells that code for the T-cell receptor. They injected normal human immune cells with the isolated T-cell receptor genes and found that the cells were then able to target cdr2-expressing human tumor cell lines and kill them. “It’s exciting,” Dr. Santomasso said, “because immunotherapy could be the magic bullet.”
Reolysin, a Virus-Based Drug
New data indicate that some sarcoma patients benefit from treatment with Reolysin, an experimental drug in phase II trials. Reolysin originated with a common, harmless virus called the reovirus. “Probably, everybody has been in contact with this virus in their life,” said Monica Mita, MD, of the Institute of Drug Development, the Cancer Therapy and Research Center at the University of Texas Health Science Center. “Nobody talks about it because patients don’t get sick from it.” Reovirus has been found to replicate itself robustly in cancer cells, destroying them, while leaving normal cells unaffected.
In a US trial that enrolled 35 patients with sarcomas that had progressed to the lungs, 21% of participants who received Reolysin experienced stable disease or tumor regression for 4 to 17 months. In addition, said Dr. Mita, Reolysin appears to be well tolerated, and adverse affects have been mild. “We have seen improvement in patients who have resumed their daily lives again,” she added.
Other studies have looked at the role some herpes viruses may play in attacking cancer cells. A 2007 study found that a manufactured herpes virus, labeled NV1020, showed promising results in colorectal patients whose disease progressed following chemotherapy.
Role for Community Oncologists
The work Dr. Santomasso and her colleagues are doing is, by their own admission, years away from practical application; the same holds for the trials being conducted with Reolysin. Nevertheless, community oncologists have an important role in investigating these agents, Dr. Mita said. “Lots of progress and research is being done, and community oncologists need to be aware of that and think about referring patients to clinical trials.”
While many oncologists are familiar with cases in which a tumor spontaneously regressed, it is not likely that the findings of the Norwegian study will result in physicians deciding not to treat invasive breast malignancies. For one thing, many questions remain about the study’s methods and conclusions. In addition, with no way to predict with certainty which tumors will disappear and which will not, the risks of delaying treatment are too great for some women.
Ed Rabinowitz is a veteran healthcare writer and reporter. He welcomes comments at firstname.lastname@example.org.