Cancer killing clue could lead to safer and more powerful immunotherapies

February 12, 2018, Walter and Eliza Hall Institute
cancer
Killer T cells surround a cancer cell. Credit: NIH

New research could help to safely adapt a new immunotherapy—currently only effective in blood cancers—for the treatment of solid cancers, such as notoriously hard-to-treat brain tumours.

The study, led by Dr. Misty Jenkins from the Walter and Eliza Hall Institute of Medical Research, explains the crucial mechanisms by which CAR-T cell is able to rapidly target and kill , and why it may cause serious side effects.

CAR-T cell therapy is an innovative form of immunotherapy that uses synthetically engineered T to redirect the patient's own immune system to fight their . Approved by the US Food and Drug Administration (FDA) in 2017, it has been successfully used to treat blood cancers such as childhood leukaemia and some lymphomas.

Unfortunately, CAR-T cell therapy has had mixed results in solid cancers, often causing significant side effects such as 'cytokine storms' - a potentially fatal inflammatory response that can lead to organ failure in some patients.

Dr. Jenkins led the study, working with collaborators Mr Alex Davenport, Associate Professor Phillip Darcy and Associate Professor Paul Neeson from the Peter Mac. It was published today in the journal Proceedings of the National Academy of Sciences.

Dr. Jenkins said the new research revealed for the first time how CAR-T cells interacted with cancer cells.

"We found that CAR-T cell receptors have the ability to rapidly identify and bind to tumour cells that would otherwise remain undetected in the immune system, and promptly kill them.

"We have previously shown a correlation between cytokine production and the length of time the were latched onto the cancer cells. The longer the cells were in contact, the more cytokines were produced, causing ever increasing degrees of damage from inflammation," she said.

Dr. Jenkins said a deep understanding of the biological factors contributing to the success and side effects of CAR-T cells would help to inform a better design and safer delivery methods for the personalised therapy.

"Our research is teaching us how to make CAR-T cells even more efficient, and without the toxic side effects, so that we can safely extend the therapy to cover a broader range of cancers," she said.

Dr. Jenkins said her research focused on how CAR-T cell therapy could successfully be used to treat . Brain cancer has some of the poorest survival rates of any cancer in the world and desperately requires new treatment approaches.

"The is an incredibly delicate and challenging environment to work within," Dr. Jenkins said.

"Brain tumours are often resistant to traditional treatments, such as chemotherapy; and surgically removing tumours can come with a lot of collateral damage.

"Finding an optimum design for CAR-T cell therapy where we can kill tumour cells with limited invasion, inflammation and side effects could significantly improve the treatment of brain cancer.

"Answering fundamental biological questions about how immune cells and cancer cells function and interact, as we have done in this study, is invaluable in the quest to find formidable treatments for fatal cancers," she said.

In 2017 Dr. Jenkins received a Carrie's Beanies 4 Brain Cancer Foundation grant and a Financial Market's Foundation for Children Grant to continue her work to develop CAR-T cell therapies and other forms of immunotherapy for treating children with brain cancer.

Explore further: Potential therapy identified for aggressive breast cancer

More information: Maria Letizia Giardino Torchia el al., "Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome," PNAS (2018). www.pnas.org/cgi/doi/10.1073/pnas.1713301115

Related Stories

Potential therapy identified for aggressive breast cancer

January 25, 2018
The European Cancer Stem Cell Research Institute, based with Cardiff University, has repurposed a current cancer therapy, TRAIL, to find a new treatment for advanced cancers that are resistant to anti-hormone therapy.

Molecular 'magnets' could improve cancer immunotherapy

February 8, 2018
Chemicals that attract specialised immune cells toward tumours could be used to develop better immunotherapies for cancer patients, according to new research published in Cell.

Virus could treat brain tumours by boosting immune system

January 3, 2018
A virus injected directly into the bloodstream could be used to treat people with aggressive brain tumours, a major new study reports.

Cancer-causing mutation suppresses immune system around tumours

December 12, 2017
Mutations in 'Ras' genes, which drive 25% of human cancers by causing tumour cells to grow, multiply and spread, can also protect cancer cells from the immune system, finds a new study from the Francis Crick Institute and ...

Potential treatment for brain cancer as drug shrinks tumours

August 14, 2017
An international team of researchers has found a drug previously approved to treat breast cancer could also be used to shrink medulloblastoma, a common form of childhood brain tumour.

Cancer can be combated with reprogrammed macrophage cells

May 20, 2016
Researchers at Karolinska Institutet have generated antibodies that reprogramme a type of macrophage cell in the tumour, making the immune system better able to recognise and kill tumour cells. The study, which is published ...

Recommended for you

Immune signature predicts asthma susceptibility

February 16, 2018
Asthma is a chronic inflammatory disease driven by the interplay of genetics, environmental factors and a diverse cast of immune cells. In their latest study, researchers at La Jolla Institute for Allergy and Immunology (LJI) ...

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Team paves the way to the use of immunotherapy to treat aggressive colon tumors

February 15, 2018
In a short space of time, immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind ...

Can our genes help predict how women respond to ovarian cancer treatment?

February 15, 2018
Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

First comparison of common breast cancer tests finds varied accuracy of predictions

February 15, 2018
Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women.

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.