Therapeutic antibody targeting of individual Notch receptors

This recent paper, published in Nature, follows the ideas covered in Ronald Levy's lecture of using antibodies to target proteins related to cancer (although in this case, the cancer in question is not B Cell Lymphoma). Receptors of the Notch family are widely expressed transmembrane proteins that function as key conduits through which mammalian cells communicate to regulate cell fate and growth. Aberrant signalling through each receptor has been linked to numerous diseases, particularly cancer, making the Notch pathway a compelling target for new drugs. The researchers have found that using antibodies to selectively block the Notch1 receptor successfully inhibits tumor growth in pre-clinical models.

http://www.nature.com/nature/journal/v464/n7291/full/nature08878.html

Immune Signatures to Predict Successful Kidney Transplants

More than half of kidney transplants from deceased donors fail within 10 years, requiring the recipient to go on dialysis or get another transplant. These failures are usually the result of immune rejection, a return of the original kidney disease, or even the effect of drugs used for immunosuppression. However, there are some recipients who, even after stopping their medications, never reject the donated kidney. Why?

Recent evidence suggests that there might be biological markers, or more critically genetic signatures, that enable some people to be less susceptible to transplant rejection. Blood tests have shown that these patients make more B cells and are more likely to have activated versions of three genes on their B cells. In addition, almost all of them lacked antibodies specifically aimed against the donated kidney. Other researchers are trying to use kidney biopsies to assess rejection risk and to develop of risk-scoring formula based on genetic features found to predict transplant failure. Thus far, their predictions have been fairly accurate.

Such immune signatures are beginning to emerge and be recognized by researchers in the lab. Slowly the predictions are becoming more accurate for who will and who won't reject a kidney transplant. The next step is to figure out a way to make such predictive information more accessible and useful to clinics to help determine which patients could be taken off their harsh immunosuppressive drugs without high risk of losing the organ.

Breast Cancer Vaccine Successful in Mice

Scientists at Ohio's Cleveland Clinic have a new vaccine in the works that they hope will prove capable of preventing breast cancer. The vaccine introduces a protein found in most breast cancers but not in healthy women, except during lactation. As is the goal of vaccines, the introduction of this protein will allow the body's immune system to recognize and target cells expressing the protein. This would allow cancerous tissue to be destroyed without damaging surrounding healthy breast tissue.

As of yet, the vaccine has only been tested in mice--the FDA will require much more rigorous testing before trials can begin in humans. However, the vaccine was able to significantly prevent the occurrence of breast cancer in the mice. Further experiments need to be done, but the hope is that one day this vaccine can be offered to women at higher risk for breast cancer, namely women over 40 and those with a genetic predisposition or family history. Dr. Vincent Tuohy, the study's principal investigator and an immunologist at the Cleveland Clinic's Lerner Research Institute believes it will take at least 10 years before the vaccine is approved, probably even more.

Influenza Vaccine for Egg-Allergic Patients-- What's safe?

The journal Pediatrics published their report entitled "Safety of Influenza Vaccine Administration in Egg-Allergic Patients." As influenza vaccine manufacturers (except for cell-culture processed vaccine manufacturers such as Novartis) use eggs to to culture the inactive virus, influenza prophylaxis is a concern for individuals with egg allergies. Current guidelines recommend that all people with egg allergies receive a skin test before getting the vaccine; as only 20-30% of the population receives the vaccine as it is, this rate is much lower for people with egg allergies with this additional requirement.

The authors of this article questioned if the current guidelines for egg-allergic people could be loosened, increasing their vaccine utilization. To do this, they conducted a retrospective chart-review study of egg-allergic patients who did receive the skin test or a two dose graded vaccine (which the authors argue can be an alternative option). They found that of the patients who first received the skin test, 95% went on to tolerate the vaccine without serious side effects. Of the 115 patients who did not receive the skin test, 97% tolerated the vaccine without serious side effects. The authors argue that this data suggests that patients with food-allergies (as long as they are without anaphylaxis to egg) can safely receive the two-dose, graded vaccine without the skin test

Do you think these findings support alteration of the current guidelines, in order to increase the rate of vaccination in this population?

Image source: http://discovermagazine.com/2009/jul-aug/27-vaccine-production-horribly-outdated-3-ways-fix-it/vaccine_egg.jpg

Article source: http://pediatrics.aappublications.org/cgi/content/full/125/5/e1024

Probiotic Cheese Boosts Immune System in Elderly

Why We Should all Start Eating More Cheese

According to a study in theFEMS Immunology & Medical Microbiology, eating probiotic cheese on a daily basis can help preserve and enhance the immune system. Because it is a carrier for probiotic bacteria, a population of elderly showed increase immunity to disease.

In the study, three different trials were run: phase I (two weeks, 15g/day) was breakfast consumption of a control cheese, phase II (four weeks 15g/day) was the intervention and participants consumed a similar cheese containing Danisco probiotics (109 CFU/dose), and phase III (four weeks) control cheese again.

The HOWARU® Rhamnosus (Lactobacillus rhamnosus HN001) and HOWARU® Dophilus (Lactobacillus acidophilus NCFM), enhanced cheese from the second phase increased phagocytic and Natural Killer cell activity and blood indicators of immune activity. This observation relates to the observed benefits of yogurt on immunity, vitamin D, and the bad effects of fatty foods that weaken the immune system.

http://www.foodproductdesign.com/news/2010/05/probiotic-cheese-boosts-immune-systems-in-elderly.aspx

Universal Flu Vaccine

Researchers at Mt. Sinai Medical School are looking into creating a universal influenza vaccine. A "headless" form of the vaccine has been tested in mince and has proven to prevent against influenzas that killed other mice. They say that with more development this technology will be applicable to humans.

Flu vaccines today allow the body to create antibodies against the "heads" of the virus as seen in the picture above. That portion of the virus is very specific and changes rapidly- which is why we get a new vaccine every year as the prevalent strain changes. The new vaccines allow the body to create vaccines against the lower portion of the hemaglutinin, which does not change as often.

"Through further development and testing, we predict that a single immunization with a headless HA vaccine will offer effective protection through several influenza epidemics," Peter Palese of Mt. Sinai Medical School stated.

The hope is that the possibility of a universal flu vaccine could open the door to other types of universal vaccines.

Read More http://www.wired.com/wiredscience/2010/05/universal-flu-vaccine/#ixzz0p3YTmVmF

New Therapeutic Target for Diabetes

Dysfunction of beta cells in the pancreas underlies diabetes onset; this dysfunction is in part initiated by inflammation mediated by cytokines. Previously, there has been a call for more research on the mechanism by which beta cells respond to cytokines if protective therapies were available.

Researchers at the Indiana University School of Medicine have done just this, identifying the role of a particular protein-- eIF5A. By depleting this specific protein, preventing it from becoming active, and blocking its modification to contain hypsusine, mice were protected from developing diabetes. The researchers, under Dr. Raghavendra G. Mirmira, found that eIF5A was involved in the production of pro-inflammatory cytokines that leads to islet dysfunction and thus diabetes onset. They propose that a new form of therapy should capitalize on these mice trials that show that eIF5A depletion and hypusination inhibition protects against glucose intolerance .

Article Source: http://www.jci.org/articles/view/38924?key=b2bc783a7aa254cd4fbd and http://www.jci.org/articles/view/38924?key=b2bc783a7aa254cd4fbd

Image Source: http://www.babble.com/CS/blogs/strollerderby/2009/02/diabetes_0.jpg