Lab mouse

First mouse with human-like immune response

USC (US) — A first-of-its-kind mouse model with an immune response system more like a human’s could speed development of drugs to treat diseases like 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 mice are not humans, and 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; but for reasons not entirely clear, the drug does not trigger the same response in people with cancer.

Scientists hypothesize that the failure to translate 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.

Now researchers have 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,” says Weiming Yuan, PhD, assistant professor of molecular microbiology and immunology at the Keck School of Medicine of the University of Southern California and principal investigator of the study published in the Proceedings of the National Academy of Sciences. “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 1 out of 100 to 1 out of 5,” Yuan says.

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.

Researchers from Yale University, the UCLA Immunogenetics Center, and Yeshiva University contributed to the  research, which was supported by the National Institutes of Health, the Harry Lloyd Charitable Trust, the Margaret Early Medical Research Trust, and the Howard Hughes Medical Institute.

Source: USC

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  1. simon

    The immune system contains a network of proteins, tissues, organs and cells that work together to defend and attack organism and other invaders, called antigens, that can harm the body. The cells involved in the immune system are called leukocytes, or white blood cells. There are two types of leukocytes, phagocytes and lymphocytes, and each has a distinct role in the immune process. The phagocytes are the cells that ingest harmful substances in the body, like dead cells, bacteria or toxins. Lymphocytes, which are either T cells or B cells, are a vital part of immune functioning as they recognize any previous contact with invading antigens. B cells create antibodies, proteins that latch onto specific antigens, neutralize the antigens, while T cells destroy them. Lymphocytes have the ability to adapt to changes in the structure of these harmful invaders.

    Originating in the lymphoid organs, which include the spleen, bone marrow and the thymus, leukocytes travel along the lymphatic vessels between the organs and the lymph nodes, where they are stored, as well as through the blood. When an antigen attacks the body, the body begins its immune response. REF & More Information at: http://www.newsonhealthcare.com/understanding-the-immune-system-a-bodys-dynamic-design-for-defense/

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