Genetically modified cells attack tumors

December 21, 2006
Lab mice

St. Jude researchers show genetically modified stem cells in the nervous system actively seek out even tiny tumors
Mice with neuroblastoma tumors have been successfully treated with genetically modified cells that sought out the cancer cells and activated a chemotherapy drug directly at those sites, according to investigators at St. Jude Children's Research Hospital and their colleagues at City of Hope National Medical Center (Duarte, Calif.) and the University of British Columbia (Vancouver, Canada). Neuroblastoma is a solid tumor that arises in the part of the nervous system outside the brain.

The researchers also showed that the modified cells migrated to tumors regardless of how small the tumors were or where they were located in the body. A report on this work appears in the Dec. 20 issue of the Web-based journal PLoS ONE.

The study is the first to provide evidence that such cells, called neural stem-progenitor cells (NSPCs), can be used to target solid tumors that have metastasized (spread from their original site), according to the researchers. During normal development NSPCs give rise to all the various types of cells in the brain.

Moreover, since the drug, called CPT-11 (irinotecan), is already used to treat cancers, doctors and scientists already know how the drug behaves in humans. That knowledge should make it easier to translate these laboratory findings to the clinic, the researchers said.

The ability to target tumors with CPT-11 suggests that this technique could let clinicians treat tumors in humans more effectively while avoiding side effects caused by damage to normal cells. The success with neuroblastoma also suggests this technique might improve the treatment of other solid tumors that metastasize, such as colon and prostate cancer.

This homing ability is especially important in the case of high-risk neuroblastoma because even very small tumors that survive after an initially successful treatment often generate more cancer cells that spread and become unresponsive to treatment, said Mary Danks, Ph.D., associate member of Molecular Pharmacology at St. Jude. Therefore, the study holds special promise for children with high-risk neuroblastoma because as many as 80 percent of these patients relapse with chemotherapy-resistant metastatic cancer. Neuroblastoma is considered high risk if the tumors have certain genetic mutations or have already spread when the cancer is diagnosed.

"Clinicians are limited in how aggressively they can treat these children because the chemotherapy drugs produce harsh side effects and therefore must be administered at reduced levels," Danks said. "But by targeting tumor cells while avoiding normal cells, doctors could treat the neuroblastoma aggressively while minimizing side effects." Danks is senior author of the PLoS ONE report.

The researchers based their new treatment on work previously reported that showed certain NSPCs have a natural tendency to seek out damaged or cancerous areas in the brain.

In the current study, the researchers first injected into mice that had neuroblastoma large numbers of NSPCs that had been genetically modified to carry a drug-activating enzyme called rabbit carboxylesterase (rCE). The NSPCs traveled to the tumors and used the gene to produce rCE. Three days later the team injected the CPT-11 into the mice. The drug dispersed throughout the mice but was activated by rCE selectively at the neuroblastoma tumors. The researchers used the rabbit form of this enzyme because it activates CPT-11 much more efficiently than the human version, Danks said. This activation is essential to treatment because the activated form is up to 1,000 times more active than CPT-11.

While half of a group of 10 mice that received only CPT-11 survived for six months, all 10 mice treated with both the modified NSPCs and CPT-11 survived for more than six months.

"There is a real need for new treatments for neuroblastoma that target tumor cells while having minimal side effects," said Karen S. Aboody, M.D., assistant professor in the Division of Hematology and Hematopoietic Cell Transplantation at City of Hope. "The use of NSPCs carrying the gene for rCE might fill that need." Aboody is first author of the PLoS ONE report.

Source: St. Jude Children's Research Hospital

Explore further: Stem cells used to build bone and fight cancer

Related Stories

Stem cells used to build bone and fight cancer

January 25, 2018
This year's Broad Clinical Research Fellows will apply stem cell-based approaches to two prevalent problems: non-healing bone injuries, which affect 5 million Americans each year, and neuroblastoma, the most common solid ...

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Old drug may have new tricks for fighting cancer

February 5, 2018
In recent years, a powerful suite of drugs known as kinase inhibitors have been developed to treat cancer and other diseases. Primary targets of such drugs include a family of receptor tyrosine kinases (RTKs) which protrude ...

Researchers identify an indirect way of countering a key genetic lesion in neuroblastoma

December 5, 2017
Pediatric cancers tend to have relatively "quiet" genomes compared to tumors in adults. They harbor fewer discrete genetic mutations, especially in genes for readily "druggable" targets (such as protein kinases). Instead, ...

Uncovering molecular targets for childhood cancer therapeutics

December 29, 2017
Neuroblastoma (NB) is the most common solid tumor found in children. It starts in some very early forms of nerve cells found in the embryo or fetus. Amplification of the gene MYCN is a well-characterized genetic alteration ...

Why do children get cancer?

December 8, 2017
Let's start with the good news. Childhood cancer is rare, and success rates for recovery are high. According to the American Cancer Society, childhood cancers make up less than 1 percent of all cancers diagnosed each year. ...

Recommended for you

Researchers discover novel mechanism linking changes in mitochondria to cancer cell death

February 20, 2018
To stop the spread of cancer, cancer cells must die. Unfortunately, many types of cancer cells seem to use innate mechanisms that block cancer cell death, therefore allowing the cancer to metastasize. While seeking to further ...

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.