This treatment is incredibly effective.
Activating T cells in tumors eliminated even distant metastases in mice, Stanford researchers found. Lymphoma patients are being recruited to test the technique in a clinical trial.
An injectable “vaccine” delivered directly to tumours in mice has been found to eliminate all traces of those tumours, cancer researchers have found – and it works on many different kinds of cancers, including untreated metastases in the same animal.
Scientists at Stanford University School of Medicine have developed the potential treatment using two agents that boost the body’s immune system, and a human clinical trial in lymphoma patients is currently underway.
“When we use these two agents together, we see the elimination of tumours all over the body,” said senior researcher, oncologist Ronald Levy.
“This approach bypasses the need to identify tumour-specific immune targets and doesn’t require wholesale activation of the immune system or customisation of a patient’s immune cells.”
Cancer immunotherapy is tricky. Because cancer cells are produced by the body, the immune system doesn’t see them as a threat the same way it sees invaders like viruses.
That’s why some cancer immunotherapy treatments focus on training the immune system to recognise cancer cells as a problem.
It’s an effective area of treatment, but one that often involves removing the patient’s immune cells from their body, genetically engineering them to attack cancer, and injecting them back in – a process that is both expensive and time-consuming.
The Stanford vaccine could be much cheaper and easier.
It doesn’t work like the vaccines you might be familiar with. Instead of a prophylactic administered prior to infection, the researchers gave it to mice that already had tumours, injecting directly into one of the affected sites.
‘Amazing, bodywide effects’
Levy is a pioneer in the field of cancer immunotherapy, in which researchers try to harness the immune system to combat cancer. Research in his laboratory led to the development of rituximab, one of the first monoclonal antibodies approved for use as an anticancer treatment in humans.
Some immunotherapy approaches rely on stimulating the immune system throughout the body. Others target naturally occurring checkpoints that limit the anti-cancer activity of immune cells. Still others, like the CAR T-cell therapy recently approved to treat some types of leukemia and lymphomas, require a patient’s immune cells to be removed from the body and genetically engineered to attack the tumor cells. Many of these approaches have been successful, but they each have downsides — from difficult-to-handle side effects to high-cost and lengthy preparation or treatment times.
“All of these immunotherapy advances are changing medical practice,” Levy said. “Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself. In the mice, we saw amazing, bodywide effects, including the elimination of tumors all over the animal.”
Cancers often exist in a strange kind of limbo with regard to the immune system. Immune cells like T cells recognize the abnormal proteins often present on cancer cells and infiltrate to attack the tumor. However, as the tumor grows, it often devises ways to suppress the activity of the T cells.
Levy’s method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site. (A microgram is one-millionth of a gram). One, a short stretch of DNA called a CpG oligonucleotide, works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of the T cells. The other, an antibody that binds to OX40, activates the T cells to lead the charge against the cancer cells. Because the two agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are “prescreened” by the body to recognize only cancer-specific proteins.
These cells get to work on the tumour, but some of the T cells then leave the site of the tumour to find and destroy other tumours in the body.
To test it, laboratory mice were transplanted with mouse lymphoma in two places, or genetically engineered to develop breast cancer.
Of the 90 mice with lymphoma, 87 were completely cured – the treatment was injected into one tumour, and both were destroyed. The remaining 3 had a recurrence of the lymphoma, which cleared up after a second treatment.
The treatment was also effective on the mice genetically engineered to develop breast cancer. Treating the first tumour often, but not always, prevented the recurrence of tumours, and increased the animals’ lifespan, the researchers said.
The team then tested mice with both lymphoma and colon cancer, injecting only the lymphoma. The lymphoma was destroyed, but the colon cancer was not. This demonstrates that T cells in tumours are specific to that kind of tumour – so the treatment isn’t without limitations.
But it does mean that immunotherapy is possible without genetically engineering cells outside the body; or, as is the case with a previous vaccine, extracting cancer RNA, treating it, injecting it into the body, and applying an electric charge to deliver it to immune cells.
Its efficacy is about to be tested, though. The clinical trial currently underway is expected to recruit 15 patients with low-grade lymphoma to see if the treatment works on humans.
If it’s effective, the treatment may be used in the future on tumours before they’re surgically extracted to help prevent metastases, or even prevent recurrences of the cancer.
“I don’t think there’s a limit to the type of tumour we could potentially treat, as long as it has been infiltrated by the immune system,” Levy said.
Unlike other cancer treatments already on the market, this method negated the need to infiltrate the animal’s whole immune system or use samples from its body. In some cancer therapies that already exist, like T-cell treatment used to combat leukemia and lymphoma, the patient’s immune cells need to be removed from the body and then are genetically altered to fight the cancerous cells before being reintroduced to a person’s system. This method is expensive, involves a lengthy treatment process and comes with a battery of rough side effects. But the new method is simpler.
“All of these immunotherapy advances are changing medical practice,” Levy said. “Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself. In the mice, we saw amazing, body-wide effects, including the elimination of tumors all over the animal.”