Featured Research

from universities, journals, and other organizations

Blood stem cells engineered to fight melanoma

Date:
January 10, 2012
Source:
University of California - Los Angeles Health Sciences
Summary:
Researchers have demonstrated for the first time that blood stem cells can be engineered to create cancer-killing T-cells that seek out and attack a human melanoma.

Researchers from UCLA's cancer and stem cell centers have demonstrated for the first time that blood stem cells can be engineered to create cancer-killing T-cells that seek out and attack a human melanoma. The researchers believe the approach could be useful in about 40 percent of Caucasians with this malignancy.

Related Articles


Done in mouse models, the study serves as the first proof-of-principle that blood stem cells, which make every type of cell found in the blood, can be genetically altered in a living organism to create an army of melanoma-fighting T-cells, said Jerome Zack, the study's senior author and a scientist with UCLA's Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

"We knew from previous studies that we could generate engineered T-cells. But would they work to fight cancer in a relevant model of human disease, such as melanoma?" asked Zack, a professor of medicine and microbiology, immunology and molecular genetics in the UCLA Life Sciences Division. "We found with this study that they do work in a human model to fight cancer, and it's a pretty exciting finding."

The study appeared Nov. 28 in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.

Researchers used a T-cell receptor -- cloned by other scientists from a cancer patient -- that seeks out an antigen expressed by a certain type of melanoma. They then genetically engineered the human blood stem-cells by importing genes for the T-cell receptor into the stem cell nucleus using a viral vehicle. The genes integrate with the cell DNA and are permanently incorporated into the blood stem cells, theoretically enabling them to produce melanoma-fighting cells indefinitely and when needed, said Dimitrios N. Vatakis, the study's first author and an assistant researcher in Zack's lab.

"The nice thing about this approach is a few engineered stem cells can turn into an army of T-cells that will respond to the presence of this melanoma antigen," Vatakis said. "These cells can exist in the periphery of the blood, and if they detect the melanoma antigen, they can replicate to fight the cancer."

In the study, the engineered blood stem cells were placed into human thymus tissue that had been implanted in the mice, allowing Zack and his team to study the human immune system reaction to melanoma in a living organism. Over about six weeks, the engineered blood stem cells developed into a large population of mature, melanoma-specific T-cells that were able to target the right cancer cells.

The mice were then implanted with two types of melanoma tumors, one that expressed the antigen complex that attracts the engineered T-cells and one that did not. The engineered cells specifically went after the antigen-expressing melanoma, leaving the control tumor alone, Zack said.

The study included nine mice. In four animals, the antigen-expressing melanomas were completely eliminated, while in the other five, these melanomas decreased in size, Zack said -- an impressive finding.

Response was assessed not only by measuring physical tumor size but by monitoring the cancer's metabolic activity using positron emission tomography (PET), which measures how much energy the cancer is "eating" to drive its growth.

"We were very happy to see that four tumors were completely gone and the rest had regressed, both by measuring their size and actually seeing their metabolic activity through PET," Zack said.

This approach to immune system engineering has intriguing implications, Zack said. T-cells can be engineered to fight disease, but their function is not long-lasting in most cases, and more engineered T-cells ultimately are needed to sustain a response. This new approach engineers the cells that give rise to the T-cells so that "fresh" cancer-killing cells could be generated when needed, perhaps protecting against cancer recurrence later.

Going forward, the team would like to test this approach in clinical trials. One possible approach would be to engineer both the peripheral T-cells and the blood stem cells that give rise to T-cells. The peripheral T-cells would serve as the front-line cancer fighters, while the blood stem cells are creating a second wave of warriors to take up the battle as the front line T-cells are losing function.

Zack said he hopes this engineered immunity approach will translate to other cancers as well, including breast and prostate cancers.

The four-year study was funded in part by the National Institutes of Health, the California Institute for Regenerative Medicine, the Caltech-UCLA Joint Center for Translational Medicine, the UCLA Center for AIDS Research and the UCLA AIDS Institute.


Story Source:

The above story is based on materials provided by University of California - Los Angeles Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. D. N. Vatakis, R. C. Koya, C. C. Nixon, L. Wei, S. G. Kim, P. Avancena, G. Bristol, D. Baltimore, D. B. Kohn, A. Ribas, C. G. Radu, Z. Galic, J. A. Zack. PNAS Plus: Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells. Proceedings of the National Academy of Sciences, 2011; 108 (51): E1408 DOI: 10.1073/pnas.1115050108

Cite This Page:

University of California - Los Angeles Health Sciences. "Blood stem cells engineered to fight melanoma." ScienceDaily. ScienceDaily, 10 January 2012. <www.sciencedaily.com/releases/2011/11/111128152418.htm>.
University of California - Los Angeles Health Sciences. (2012, January 10). Blood stem cells engineered to fight melanoma. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2011/11/111128152418.htm
University of California - Los Angeles Health Sciences. "Blood stem cells engineered to fight melanoma." ScienceDaily. www.sciencedaily.com/releases/2011/11/111128152418.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Christmas Kissing Good for Health

Christmas Kissing Good for Health

Reuters - Innovations Video Online (Dec. 22, 2014) Scientists in Amsterdam say couples transfer tens of millions of microbes when they kiss, encouraging healthy exposure to bacteria. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins