Targeted Immune Cells Shrink Tumors in Mice

February 10, 2009,

(PhysOrg.com) -- Researchers have generated altered immune cells that are able to shrink, and in some cases eradicate, large tumors in mice. The immune cells target mesothelin, a protein that is highly expressed, or translated in large amounts from the mesothelin gene, on the surface of several types of cancer cells. The approach, developed by researchers at the University of Pennsylvania School of Medicine and the National Cancer Institute (NCI), shows promise in the development of immunotherapies for certain tumors. The study appears online this week in the Proceedings of the National Academy of Sciences.

Expression of mesothelin is normally limited to the cells that make up the protective lining (mesothelium) of the body's cavities and internal organs. However, the protein is abundantly expressed by nearly all pancreatic cancers and mesotheliomas and by many ovarian and non-small-cell lung cancers. Although the biological function of mesothelin is not known for certain, it is thought to play a role in the growth and metastatic spread of the cancers that express it.

"Since tumor cells are derived from the body's normal cells, the immune system often does not recognize tumor molecules as dangerous or foreign and does not mount a strong attack against them," said Ira Pastan, M.D., chief of the Laboratory of Molecular Biology in NCI's Center for Cancer Research, a study collaborator. Moreover, even though it is possible to genetically engineer immune system cells to recognize molecules on tumor cells, most of the molecules found on tumor cells are also found on normal cells. But, Pastan notes, "Mesothelin is a promising candidate for generating tumor-targeting T cells, given its limited expression in normal tissues and high expression in several cancers."

Previous laboratory research has shown that certain immune system cells, called T cells, can kill tumor cells that express mesothelin. In addition, studies in both animals and humans have shown that antibodies directed against mesothelin protein can shrink tumors.

In the new study, the research team genetically engineered human T cells to target human mesothelin. To produce them, a modified virus was used as a delivery vehicle, or vector, to transfer synthetic genes to T cells. These genes directed the production of hybrid, or chimeric, proteins that can recognize and bind to mesothelin and consequently stimulate the proliferation and cell-killing activity of the T cells. In laboratory studies, the team found that the engineered T cells proliferated and secreted multiple cytokines when exposed to mesothelin. Cytokines are proteins that help control immune functions. The cells also expressed proteins that made them resistant to the toxic effects of tumors and their surrounding tissues.

To study the effects of the engineered T cells on tumor tissue, the researchers implanted human mesothelioma cells underneath the skin of mice. About six weeks later, when tumors had formed and progressed to an advanced stage, the engineered T cells were administered to the mice. Direct injection of the T cells into tumors or into veins of the mice resulted in disappearance or shrinkage of the tumor.

"Based on the size of the tumors and the number of cells administered, we estimate that one mesothelin-targeted T cell was able to kill about 40 tumor cells," said study leader Carl H. June, M.D., Professor of Pathology and Laboratory Medicine and director of Translational Research at Penn's Abramson Cancer Center. "This finding indicates that small doses of these cells may have potential in treating patients with large tumors. Clinical trials are being developed to investigate this approach in patients with mesothelioma and ovarian cancer."

Source: University of Pennsylvania School of Medicine

Explore further: New therapeutic gel shows promise against cancerous tumors

Related Stories

New therapeutic gel shows promise against cancerous tumors

February 21, 2018
Scientists at the UNC School of Medicine and NC State have created an injectable gel-like scaffold that can hold combination chemo-immunotherapeutic drugs and deliver them locally to tumors in a sequential manner. The results ...

Team develops new technology platform for cancer immunotherapy

February 22, 2018
Johns Hopkins researchers have invented a new class of immunotherapeutic agents that are more effective at harnessing the power of the immune system to fight cancer. Their approach results in significant inhibition of tumor ...

Researchers discover new approach to stimulate an immune response against tumor cells

January 30, 2018
New drugs that activate the immune system to target cancer cells have improved the lives of many patients with cancer. However, immunotherapies are not effective in all patients, and the success of these therapies depends ...

Cancer 'vaccine' eliminates tumors in mice, researchers find

January 31, 2018
Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers ...

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 ...

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 ...

Recommended for you

Fabric imbued with optical fibers helps fight skin diseases

February 23, 2018
A team of researchers with Texinov Medical Textiles in France has announced that their PHOS-ISTOS system, called the Fluxmedicare, is on track to be made commercially available later this year. The system consists of a piece ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Breakthrough could lead to better drugs to tackle diabetes and obesity

February 22, 2018
Breakthrough research at Monash University has shown how different areas of major diabetes and obesity drug targets can be 'activated', guiding future drug development and better treatment of diseases.

Fertility breakthrough: New research could extend egg health with age

February 22, 2018
Women have been told for years that if they don't have children before their mid-30s, they may not be able to. But a new study from Princeton University's Coleen Murphy has identified a drug that extends egg viability in ...

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.