Fighting cancer with the power of immunity

October 24, 2016, Massachusetts Institute of Technology
T cells -- immune cells that are targeted to find and destroy a particular antigen -- are key to the adaptive immune response. In this image, the top row shows few T cells in untreated mice, while the bottom rows show many T cells produced after immunotherapy treatment. Credit: Massachusetts Institute of Technology

Harnessing the body's own immune system to destroy tumors is a tantalizing prospect that has yet to realize its full potential. However, a new advance from MIT may bring this strategy, known as cancer immunotherapy, closer to becoming reality.

In the new study, the researchers used a combination of four different therapies to activate both of the immune system's two branches, producing a coordinated attack that led to the complete disappearance of large, in mice.

"We have shown that with the right combination of signals, the endogenous immune system can routinely overcome large immunosuppressive tumors, which was an unanswered question," says Darrell Irvine, a professor of biological engineering and of materials science and engineering, and a member of MIT's Koch Institute for Integrative Cancer Research.

This approach, which could be used to target many different types of cancer, also allows the immune system to "remember" the target and destroy new cancer that appear after the original treatment.

Irvine and Dane Wittrup, the Carbon P. Dubbs Professor of Chemical Engineering and Bioengineering and a member of the Koch Institute, are the senior authors of the study, which appears in the Oct. 24 online edition of Nature Medicine. The paper's lead authors are MIT graduate student Kelly Moynihan and recent MIT PhD recipient Cary Opel.

Multipronged attack

Tumor cells often secrete chemicals that suppress the immune system, making it difficult for the body to attack tumors on its own. To overcome that, scientists have been trying to find ways to provoke the immune system into action, with most focusing their efforts on one or the other of the two arms of immunity—the innate immune system and the adaptive immune system.

The innate system consists of nonspecific defenses such as antimicrobial peptides, inflammation-inducing molecules, and cells such as macrophages and . Scientists have tried to get this system to attack tumors by delivering antibodies that latch onto and recruit the other cells and chemicals needed for a successful attack.

Last year, Wittrup showed that delivering antibodies and IL-2, a signaling molecule that helps to boost immune responses, could halt the growth of aggressive melanoma tumors in mice for as long as the treatment was given. However, this treatment worked much better when the researchers also delivered T cells along with their antibody-IL2 therapy. T cells—immune cells that are targeted to find and destroy a particular antigen—are key to the immune system's second arm, the adaptive system.

Around the same time, Irvine's lab developed a new type of T cell vaccine that hitches a ride to the lymph nodes by latching on to the protein albumin, found in the bloodstream. Once in the lymph nodes, these vaccines can stimulate production of huge numbers of T cells against the vaccine target.

After both of those studies came out, Irvine and Wittrup decided to see if combining their therapies might produce an even better response.

"We had this really good lymph-node-targeting vaccine that will drive very strong adaptive immunity, and they had this combination that was recruiting innate immunity very efficiently," Irvine says. "We wondered if we could bring these two together and try to generate a more integrated immune response that would bring together all arms of the against the ."

The resulting treatment consists of four parts: an antibody targeted to the tumor; a vaccine targeted to the tumor; IL-2; and a molecule that blocks PD1, a receptor found on T cells. Each of these molecules plays a critical role in enhancing the overall immune response to the tumor. Antibodies stimulate the recruitment of additional immune cells that help to activate T cells; the vaccine stimulates proliferation of T cells that can attack the tumor; IL-2 helps the T cell population to expand quickly; and the anti-PD1 molecule helps T cells stay active longer.

Tumor elimination

The researchers tested this combination treatment in mice that were implanted with three different types of tumors—melanoma, lymphoma, and breast cancer. These types of engineered tumors are much more difficult to treat than human tumors implanted in mice, because they suppress the against them.

The researchers found that in all of these strains of mice, about 75 percent of the tumors were completely eliminated. Furthermore, six months later, the researchers injected tumor cells into the same mice and found that their immune systems were able to completely clear the tumor cells.

"To our knowledge, nobody has been able to take tumors that big and cure them with a therapy consisting entirely of injecting biomolecular drugs instead of transplanting T cells," Wittrup says.

Using this approach as a template, researchers could substitute other types of antibodies and vaccines to target different tumors. Another possibility that Irvine's lab is working on is developing treatments that could be used against tumors even when scientists don't know of a specific vaccine target for that type of tumor.

Explore further: New anti-cancer strategy mobilizes both innate and adaptive immune response

More information: Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses,Nature Medicine, nature.com/articles/doi:10.1038/nm.4200

Related Stories

New anti-cancer strategy mobilizes both innate and adaptive immune response

July 1, 2016
Though a variety of immunotherapy-based strategies are being used against cancer, they are often hindered by the inability of the immune response to enter the immunosuppressive tumor microenvironment and to effectively mount ...

Stimulating both major branches of the immune system halts tumor growth more effectively

April 14, 2015
The human immune system is poised to spring into action at the first sign of a foreign invader, but it often fails to eliminate tumors that arise from the body's own cells. Cancer biologists hope to harness that untapped ...

Immune checkpoint blockade improves antitumor vaccine response in mouse glioblastoma model

July 7, 2016
Glioblastoma has an extremely poor prognosis, and there is a critical need for new therapies to treat the disease. Immunotherapy helps the immune system destroy cancer cells, and recent clinical evaluation of an immune cell-based ...

Parasite proteins prompt immune system to fight off ovarian tumors in mice

July 22, 2016
Scientists identified the specific proteins secreted by the parasite Toxoplasma gondii that cause the immune system in mice to attack established ovarian tumors. The study, led by David Bzik of the Geisel School of Medicine ...

Killer T cells recognize cancer in pre-clinical tumors, but are silenced as tumor develops

August 9, 2016
One of the challenges for developing truly successful immunotherapies is that cancer is a wily foe for the immune system. Tumors have multiple lines of defense against our immune cells' attempts to attack them. Although our ...

Study identifies a potential therapeutic target for lung cancer

June 13, 2016
Small-cell lung cancer (SCLC) is one of the deadliest types of cancer, and it has been several decades since new treatment options have been approved for this disease. Although recent advances in cancer treatments have focused ...

Recommended for you

Single-cell study in a childhood brain tumor affirms the importance of context

April 20, 2018
In defining the cellular context of diffuse midline gliomas, researchers find the cells fueling their growth and suggest a potential approach to treating them: forcing their cells to be more mature.

Aggressive breast cancer already has resistant tumour cells prior to chemotherapy

April 20, 2018
Difficult to treat and aggressive "triple-negative" breast cancer is chemoresistant even before chemotherapy begins, a new study by researchers from Karolinska Institutet and the University of Texas MD Anderson Cancer Center ...

Mechanism that drives development of liver cancer brought on by non-alcoholic fatty liver disease discovered

April 19, 2018
A team of researchers from several institutions in China has found a mechanism that appears to drive the development of a type of liver cancer not caused by alcohol consumption. In their paper published in the journal Science ...

Discovery adds to evidence that some children are predisposed to develop leukemia

April 19, 2018
St. Jude Children's Research Hospital researchers have made a discovery that expands the list of genes to include when screening individuals for possible increased susceptibility to childhood leukemia. The finding is reported ...

Scientists identify 170 potential lung cancer drug targets using unique cellular library

April 19, 2018
After testing more than 200,000 chemical compounds, UT Southwestern's Simmons Cancer Center researchers have identified 170 chemicals that are potential candidates for development into drug therapies for lung cancer.

Chip-based blood test for multiple myeloma could make bone biopsies a relic of the past

April 19, 2018
The diagnosis and treatment of multiple myeloma, a cancer affecting plasma cells, traditionally forces patients to suffer through a painful bone biopsy. During that procedure, doctors insert a bone-biopsy needle through an ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.