Featured Research

from universities, journals, and other organizations

Scientists design mouse with more human-like immune response

Date:
February 4, 2013
Source:
University of Southern California, Keck School of Medicine
Summary:
Scientists have genetically engineered a mouse to more closely mimic a human immune response. The transgenic mouse exhibits humanized CD1d molecules, naturally occurring molecules that activate an especially potent white blood cell called the natural killer T cell. The mouse model has the potential to accelerate development of human immunotherapies for diseases like cancer, diabetes and tuberculosis.

Medical scientists at USC have bred a first-of-its-kind mouse model that possesses an immune response system more like that of a human's. The discovery makes way for quicker and more cost-effective development of next-generation drugs to treat human diseases, such as cancer, diabetes and tuberculosis.

Medical researchers have long used mice and rats to help formulate new drugs and vaccines, in part because their genetic and biological characteristics closely parallel human physiology. But many experimental drugs that work extraordinarily well in rodents fail miserably when tested in people.

One such drug, α-galactosylceramide (α-GalCer), essentially wipes out cancerous tumors in mice by activating the body's immune system; for reasons not entirely clear, the drug does not trigger the same response in people with cancer. Scientists hypothesize that this failure is due to subtle differences between the CD1d molecules in mice and humans and how they respond to tumors and infection. CD1d molecules are found on certain cells that trigger the body's innate immune response.

In a study to be published this week by the Proceedings of the National Academy of Sciences, USC researchers describe how they genetically engineered mice to express CD1d molecules that look more like those in humans and in more similar proportions. More importantly, the humanized CD1d molecules effectively trigger natural killer T (NKT) cells -- a recently discovered type of white blood cell that attacks tumors and infection -- in live animals when exposed to α-GalCer.

"It's the best model we have in the field," said Weiming Yuan, assistant professor of molecular microbiology and immunology at the Keck School of Medicine of USC and principal investigator of the study. "We've basically set a platform to fast-track the identification of immunotherapies that can kill cancer and also make vaccines stronger."

Once activated, NKT cells react in a matter of hours whereas other T cells may take days. This rapid response makes them difficult to study but also an ideal target for drug-makers. Yuan's humanized mouse allows scientists to more accurately test the viability of those NKT cell-targeting drugs before going to human clinical trials.

"Before, it would have been a guess as to whether the drug would work in people. Now, the chance of success goes from one out of 100 to one out of five," Yuan said.

Yuan and colleagues have yet to demonstrate the effects of inserting a more human-like version of the final component of the CD1d/NKT system, the T cell receptor. More experiments are necessary to determine why α-GalCer is ineffective in treating people with cancer and to develop novel α-GalCer derivatives that work with the human immune system.

Co-authors included Xiangshu Wen, Seil Kim and Agnieszka Lawrenczyk of the Keck School; Ping Rao of the UCLA Immunogenetics Center and Department of Pathology; Leandro Carreρo and Steven Porcelli of the Albert Einstein College of Medicine at Yeshiva University; and Peter Cresswell of the Yale University School of Medicine.

The research was supported by the National Institutes of Health (R01 AI091987, R01 AI059167, R01 AI045889), the Harry Lloyd Charitable Trust, the Margaret Early Medical Research Trust and the Howard Hughes Medical Institute.


Story Source:

The above story is based on materials provided by University of Southern California, Keck School of Medicine. The original article was written by Alison Trinidad. Note: Materials may be edited for content and length.


Journal Reference:

  1. X. Wen, P. Rao, L. J. Carreno, S. Kim, A. Lawrenczyk, S. A. Porcelli, P. Cresswell, W. Yuan. Human CD1d knock-in mouse model demonstrates potent antitumor potential of human CD1d-restricted invariant natural killer T cells. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1300200110

Cite This Page:

University of Southern California, Keck School of Medicine. "Scientists design mouse with more human-like immune response." ScienceDaily. ScienceDaily, 4 February 2013. <www.sciencedaily.com/releases/2013/02/130204153708.htm>.
University of Southern California, Keck School of Medicine. (2013, February 4). Scientists design mouse with more human-like immune response. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2013/02/130204153708.htm
University of Southern California, Keck School of Medicine. "Scientists design mouse with more human-like immune response." ScienceDaily. www.sciencedaily.com/releases/2013/02/130204153708.htm (accessed July 29, 2014).

Share This




More Plants & Animals News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rodents Rampant in Gardens Around Louvre

Rodents Rampant in Gardens Around Louvre

AP (July 29, 2014) — Food scraps and other items left on the grounds by picnickers brings unwelcome visitors to the grounds of the world famous and popular Louvre Museum in Paris. (July 29) Video provided by AP
Powered by NewsLook.com
Jane Goodall Warns Great Apes Face Extinction

Jane Goodall Warns Great Apes Face Extinction

AFP (July 29, 2014) — The world's great apes face extinction within decades, renowned chimpanzee expert Jane Goodall warned Tuesday in a call to arms to ensure man's closest relatives are not wiped out. Duration: 00:58 Video provided by AFP
Powered by NewsLook.com
How Your Face Can Leave A Good Or Bad First Impression

How Your Face Can Leave A Good Or Bad First Impression

Newsy (July 29, 2014) — Researchers have found certain facial features can make us seem more attractive or trustworthy. Video provided by Newsy
Powered by NewsLook.com
Rat Infestation at Paris' Tuileries Garden

Rat Infestation at Paris' Tuileries Garden

AFP (July 29, 2014) — An infestation of rats is causing concern among tourists at Paris' most famous park -- the Tuileries garden next to the Louvre Museum. Duration: 00:54 Video provided by AFP
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