Nav: Home

Engineering non-immune cells to kill cancer cells

November 13, 2017

T-cells are one of the immune system's major weapons. They detect the body's cells infected with a virus and trigger their ablation, effectively killing the virus. T-cells cannot do the same with cancer cells, however, as they do not recognise them as foreign cells and are therefore unable to eliminate them.

But researchers have recently used T-cells engineered in the laboratory to combat tumours. Modified to include additional functions, these immune cells can hunt down and kill cancer cells. Unfortunately, however, such immune cell therapies can have significant side-effects. On top of that, the production of modified T-cells is technically challenging. Now a team of researchers led by ETH Professor Martin Fussenegger from the Department of Biosystems Science and Engineering (D-BSSE) in Basel has come up with an innovative and simplified approach for producing therapeutically effective synthetic designer cells to combat cancer. The researchers have built three additional components into human renal cells and (adipose) stem cells, thereby transforming them into synthetic designer cells that mimic T-cells.

One of the components of synthetic T-cells entails molecular antennae protruding well outside the membrane. Also embedded within the cell membrane are antibodies with specific docking sites, which can sense the target structures of the cancer cell and bind to them. The third component is a gene network that generates a molecule complex. This molecule complex comprises a molecular "warhead" that penetrates the membrane of the target cell. It is linked to a converter molecule that activates an anti-cancer substance in the tumour cell's interior.

The precursor of this active substance needs to be added to the system externally. Cancer cells absorb this substance, and the converter module transforms it from an inactive to inactive state. The cancer cells bursts, the active substance is released and destroys other tumour cells in the "death zone" around the synthetic T-cell. "This bystander effect makes our synthetic T-cells even more effective," Professor Fussenegger explains.

Mechanical trigger

The mechanism triggering the signal cascade leading to the destruction of the cancer cell is new, and has a physical function: as the synthetic T-cell moves closer towards the target cell, the antennae proteins buckle. The antennae's anchorage deep within the cell therefore loses contact with a molecular switch that it had previously blocked. As a response to the "ON" command, a signal cascade is initiated which actuates the production of the molecule complex.

The new type of artificial T-cell has several advantages over current cancer treatments. Whereas during chemotherapy the body is flooded with active substances in order to kill as many rapidly dividing cells as possible in a very unselective manner, only a few artificial T-cells are needed in the new therapy. What's more, these are only deployed locally and in a carefully targeted fashion. "Our innovative T-cells may detect and kill metastasising cancer cells at a very early stage, when other treatments are not effective," Professor Fussenegger says. Another benefit: "The artificial T-cells operate totally independently from the body's immune system, enabling it to continue to function perfectly normally, so that fewer side-effects are likely."

In addition, the modular design of the system allows it to be expanded. Researchers can equip the artificial killer cells with different types of docking sites that bond to other types of cancer cells. For the current study, just published in the journal Nature Chemical Biology, scientists used docking sites that detect only one specific type of mammalian cancer cell. "This technology provides us with an enormous degree of generalisation that cannot be achieved with the genuine T-cells used in current cancer therapies," Fussenegger stresses.

It's still not clear whether - and how - this system will function in the human body. So far, ETH researchers have only tested their new cells in cell cultures. "At present our new system is still a long way from a therapeutic application," says the ETH professor. "But I believe we have opened up a new front in the battle against cancer."
-end-


ETH Zurich

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:

The Emperor of All Maladies: A Biography of Cancer
by Siddhartha Mukherjee (Author)

The Cancer-Fighting Kitchen, Second Edition: Nourishing, Big-Flavor Recipes for Cancer Treatment and Recovery
by Rebecca Katz (Author), Mat Edelson (Author)

F*ck Cancer: A totally inappropriate self-affirming adult coloring book (Totally Inappropriate Series) (Volume 4)
by Jen Meyers (Author)

Anticancer: A New Way of Life
by David Servan-Schreiber MD PhD (Author)

Radical Remission: Surviving Cancer Against All Odds
by Kelly A. Turner PhD (Author)

The Metabolic Approach to Cancer: Integrating Deep Nutrition, the Ketogenic Diet, and Nontoxic Bio-Individualized Therapies
by Dr. Nasha Winters ND FABNO L.Ac Dipl.OM (Author), Jess Higgins Kelley MNT (Author), Kelly Turner (Foreword)

The Cancer Revolution: A Groundbreaking Program to Reverse and Prevent Cancer
by Leigh Erin Connealy (Author)

Chris Beat Cancer: A Comprehensive Plan for Healing Naturally
by Chris Wark (Author)

Cancer: Step Outside the Box
by Ty M. Bollinger (Author)

Outside the Box Cancer Therapies: Alternative Therapies That Treat and Prevent Cancer
by Dr. Mark Stengler (Author), Dr. Paul Anderson (Author)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Hacking The Law
We have a vision of justice as blind, impartial, and fair — but in reality, the law often fails those who need it most. This hour, TED speakers explore radical ways to change the legal system. Guests include lawyer and social justice advocate Robin Steinberg, animal rights lawyer Steven Wise, political activist Brett Hennig, and lawyer and social entrepreneur Vivek Maru.
Now Playing: Science for the People

#495 Earth Science in Space
Some worlds are made of sand. Some are made of water. Some are even made of salt. In science fiction and fantasy, planet can be made of whatever you want. But what does that mean for how the planets themselves work? When in doubt, throw an asteroid at it. This is a live show recorded at the 2018 Dragon Con in Atlanta Georgia. Featuring Travor Valle, Mika McKinnon, David Moscato, Scott Harris, and moderated by our own Bethany Brookshire. Note: The sound isn't as good as we'd hoped but we love the guests and the conversation and we wanted to...