Nav: Home

Fighting cancer with the power of immunity

October 24, 2016

CAMBRIDGE, MA -- 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, aggressive tumors 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 cells 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 natural killer cells. Scientists have tried to get this system to attack tumors by delivering antibodies that latch onto tumor cells 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 immune system against the tumor."

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 immune response 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.
-end-
The research was funded by the Koch Institute support core grant from the National Cancer Institute, the National Institutes of Health, the Bridge Project partnership between the Koch Institute and the Dana-Farber/Harvard Cancer Center, the V Foundation, and the Ragon Institute of MGH, MIT, and Harvard.

Massachusetts Institute of Technology

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...