Featured Research

from universities, journals, and other organizations

Immune-cell therapy could strengthen promising melanoma treatment

Date:
March 22, 2013
Source:
University of California - Los Angeles
Summary:
Scientists have used newly developed nanotechnology chips (multidimensional and multiplexed immune monitoring assays) to successfully monitor T cells genetically engineered to attack melanoma. They have discovered that the T cells change over time when returned to patients. These results will help improve engineered immunotherapy for melanoma and the assays will help understand a spectrum of other cellular immunotherapies in the future.

A new study of genetically modified immune cells by scientists from UCLA and the California Institute of Technology could help improve a promising treatment for melanoma, an often fatal form of skin cancer.

The research, which appears March 21 in the advance online edition of the journal Cancer Discovery, was led by James Heath, a member of UCLA's Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research and UCLA's Jonsson Comprehensive Cancer Center. Heath is a professor of molecular and medical pharmacology at UCLA and also holds the Elizabeth W. Gilloon Chair in Chemistry at Caltech.

The melanoma treatment uses T cells -- immune cells that play a major role in fighting infection -- taken from patients with melanoma. The cells are then genetically modified in the laboratory so that when they are reintroduced into a patient's bloodstream, they specifically attack melanoma tumors. In early clinical trials, this treatment was shown to shrink tumors dramatically in many patients, but the positive effects were often short-lived.

The UCLA and Caltech researchers found that after the engineered T cells were returned to patients, their efficacy faded within two to three weeks. Surprisingly, however, once the engineered cells were no longer effective, a new group of non-engineered T cells arose that had a similar tumor-killing effect that lasted even longer, the scientists discovered.

Using newly developed nanotechnology chips to perform multidimensional and multiplexed immune-monitoring assays, the researchers were able to examine at high resolution single engineered T cells taken at different times from patients undergoing the therapy, each of whom had a different level of response to the treatment.

"The engineered T cells did not recover their tumor-killing effect," Heath said, "but after one month, another group of T cells appeared that did have tumor-killing effects for another 90 days. Those were not the genetically engineered T cells, and they appeared to be a byproduct of a process called 'antigen spreading' by the original engineered cells. After 90 days, those cells lost their tumor-killing ability as well."

Antigen spreading is a process by which a T cell that has been engineered to attack a particular tumor expands its immune response to other T cells in the body, which then attack the same tumor but are focused on different antigens. (Antigens are substances that trigger a response by the body's immune system.) Scientists may be able to use this process, Heath stressed, to improve T cell-based treatments for melanoma.

"Our results have led us to possible ways to improve the T cell therapy to extend its positive effect," Heath said. "We need to incorporate strategies that maintain the functional properties of the engineered T cells used for therapy. This might include modifying how we grow the T cells in the laboratory to make their tumor-killing effect last longer or make them resistant to the effects of the patient's T cells as they recover from pretreatment chemotherapy conditioning and possibly increase the antigen spreading of anti-tumor T cells."

UCLA professor of medicine Dr. Antoni Ribas was one of Heath's key collaborators on the research.

"One of the possible approaches to resolve the problem identified by this study is to use engineered blood stem cells -- instead of the peripheral blood used in the original trials -- with this therapy in the hope that the engineered blood stem cells will provide a renewable source of engineered T cells," said Ribas, a member of UCLA's Broad Stem Cell Research Center and Jonsson Cancer Center.

Caltech's Chao Ma, the study's first author, said the findings and the use of the new nanotechnology assay process hold promise for treatments of other disease as well.

"This study points to the value of these single-cell functional analyses for probing the successes and failures of a sophisticated immunotherapy," he said. "I am excited to see its use as a monitoring tool to understand a spectrum of other cellular immunotherapies in the near future."

This research was funded by the National Cancer Institute, the Jean Perkins Foundation, The California Institute for Regenerative Medicine, UCLA's Broad Stem Cell Research Center, the Seaver Institute, the PhaseOne Foundation, the Garcia-Corsini Family Fund, the Caltech/UCLA Joint Center for Translational Medicine, the Melanoma Research Alliance, a Rosen Fellowship and UCLA's Jonsson Comprehensive Cancer Center.


Story Source:

The above story is based on materials provided by University of California - Los Angeles. The original article was written by Shaun Mason. Note: Materials may be edited for content and length.


Journal Reference:

  1. C. Ma, A. F. Cheung, T. Chodon, R. C. Koya, Z. Wu, C. Ng, E. Avramis, A. J. Cochran, O. N. Witte, D. Baltimore, B. Chmielowski, J. S. Economou, B. Comin-Anduix, A. Ribas, J. R. Heath. Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy. Cancer Discovery, 2013; DOI: 10.1158/2159-8290.CD-12-0383

Cite This Page:

University of California - Los Angeles. "Immune-cell therapy could strengthen promising melanoma treatment." ScienceDaily. ScienceDaily, 22 March 2013. <www.sciencedaily.com/releases/2013/03/130322104324.htm>.
University of California - Los Angeles. (2013, March 22). Immune-cell therapy could strengthen promising melanoma treatment. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2013/03/130322104324.htm
University of California - Los Angeles. "Immune-cell therapy could strengthen promising melanoma treatment." ScienceDaily. www.sciencedaily.com/releases/2013/03/130322104324.htm (accessed April 18, 2014).

Share This



More Health & Medicine News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
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:
from the past week

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