RxPG News Feed for RxPG News

Medical Research Health Special Topics World
 Asian Health
 Food & Nutrition
 Men's Health
 Mental Health
 Occupational Health
 Public Health
 Sleep Hygiene
 Women's Health
 Canada Healthcare
 China Healthcare
 India Healthcare
 New Zealand
 South Africa
 World Healthcare
   Latest Research
 Alternative Medicine
  Bone Cancer
  Breast Cancer
  Cervical Cancer
  Gastric Cancer
  Liver Cancer
  Nerve Tissue
  Ovarian Cancer
  Pancreatic Cancer
  Prostate Cancer
  Rectal Cancer
  Renal Cell Carcinoma
  Risk Factors
  Testicular Cancer
 Clinical Trials
 Infectious Diseases
 Sports Medicine
   Medical News
 Awards & Prizes
   Special Topics
 Odd Medical News

Last Updated: Oct 11, 2012 - 10:22:56 PM
Therapy Channel

subscribe to Therapy newsletter
Latest Research : Cancer : Therapy

   EMAIL   |   PRINT
How antigen presenting cells are crucial to graft-versus-leukemia's cancer-killing effect

Oct 17, 2005 - 7:30:00 PM
"We found that without functional APCs to process and present antigens to T cells, there is no graft-versus-leukemia response, and the cancer is likely to return. GVHD occurs when the donor's immune cells attack the patient's skin, liver and gastrointestinal tract. It triggers a massive inflammatory reaction that can kill the patient, especially if he or she is older or has other medical problems."

[RxPG] Researchers at the University of Michigan's Comprehensive Cancer Center have discovered the secret weapon behind the most powerful form of cancer immunotherapy known to medicine.

Scientists call it the graft-versus-leukemia effect, and it occurs when new immune cells from donated bone marrow, called the graft, attack malignant cells in the patient and destroy them. This intense immune reaction between donor and host cells, which follows a bone marrow transplant from a healthy donor, has saved the lives of thousands of patients with leukemia, lymphoma and other types of blood and immune system cancers.

In a study to be published Oct. 16 in the advanced online edition of Nature Medicine, U-M scientists describe how antigen presenting cells are crucial to graft-versus-leukemia's cancer-killing effect.

The discovery is significant, because it could help make cellular immunotherapy safer, more effective and an option for more cancer patients – especially those for whom a donor is unavailable or those who cannot tolerate the procedure's side-effects.

"We already knew that donor T cells were important for an effective GVL response, but now we know there's another cell – the antigen presenting cell or APC – which plays a critical role in the process," says James L.M. Ferrara, M.D., who directs the U-M Cancer Center's Blood and Marrow Transplant Program.

Antigen presenting cells are rare immune system cells, which look something like a starfish. Their job is to digest proteins called antigens from foreign cells or pathogens and present them to T cells. This alerts the immune system to prepare to fight the invader. When APCs present cancer cell proteins to T cells, the T cells are primed to attack the cancer.

"We found that without functional APCs to process and present antigens to T cells, there is no graft-versus-leukemia response, and the cancer is likely to return," says Pavan R. Reddy, M.D., an assistant professor of internal medicine in the University of Michigan Medical School, who led the research study.

According to Reddy, the research results suggest that manipulating the number and activity of APCs could improve the GVL response, while reducing the risk of a common post-transplant complication called graft-versus-host disease, or GVHD.

"GVHD occurs when the donor's immune cells attack the patient's skin, liver and gastrointestinal tract," Reddy explains. "It triggers a massive inflammatory reaction that can kill the patient, especially if he or she is older or has other medical problems."

In an effort to eliminate GVHD, other researchers have suggested removing APCs from transplanted donor cells, according to Ferrara. "We know that APCs are involved in graft-versus-host disease, so people say let's take out the APCs and then we will get the anti-cancer effect without the risk of GVHD," he explains. "This paper says, no, you can't do that.

"There's a tight link between the graft-versus-leukemia effect and graft-versus-host disease," Ferrara says. "Few patients get the beneficial effects of GVL without some degree of the toxic side effects of GVHD. But if we can find ways to reduce GVHD's toxic effects, immunotherapy could become a viable option for many more cancer patients."

To study what happens during the graft-versus-leukemia effect, Reddy and his U-M colleagues used high doses of radiation to destroy the blood and immune systems of genetically different laboratory mice. After reconstituting each animal's immune system, using either functional or non-functional APCs, the mice were inoculated with cancer cells and given a bone marrow transplant that could cure the cancer. The scientists then determined which mice died from acute graft-versus-host disease, which mice died from cancer and which mice generated a GVL response to destroy the cancer cells.

"The donor and host mice were paired in ways to make their antigen-presenting cells dysfunctional, either because they were of the same tissue type as the donor, or because they had a mutation that prevented them from displaying tumor antigens to T cells," Reddy explains. "Essentially we created animals where the tumor was the same, the antigens were the same, donor T cells were the same, but the APC was dysfunctional. Without a functioning APC, there was no graft-versus-leukemia effect."

Other researchers have suggested that tumor cells can present antigens to T cells directly to stimulate an immune response against cancer, but results from the U-M study indicate the response is too weak to be effective.

"APCs shred proteins, or antigens, from cancer cells and display those shredded proteins on their surface," Ferrara says. "Cancer cells have the same proteins, but haven't gone through the APC's shredding process. It's as if APCs are master chefs who prepare the antigens in a way to make them especially delicious to T cells. So instead of taking just one bite, they go back for seconds or thirds."

In future research, U-M scientists will explore how to manipulate APC function in ways that will preserve their vital role in stimulating an immune response against cancer, while controlling the intensity of graft-versus-host disease. Reddy and Ferrara have studied drugs called HDAC inhibitors and found that they modulate APC function in mice. They hope to design an initial study of these drugs in post-transplant leukemia patients within a year.

Publication: Oct. 16 advanced online edition of Nature Medicine
On the web: www.med.umich.edu 

Advertise in this space for $10 per month. Contact us today.

Related Therapy News
Taccalonolides from bat plants selectively kill cancer cells
Photodynamic therapy can help preserve the voice for patients with early stage laryngeal cancer
Bionic Nose to Detect Cancers
Anti- cancer gene discovered- new strategy for treatment?
Anthracycline induced heart damage can be reduced by prolonging infusion time
Genomic signatures to guide the use of chemotherapeutics
CDK2/FOXO1 as drug target to Prevent Tumors
Telomerase inhibitors may revolutionize cancer therapy
First ever shots of the cervical cancer vaccine administered in Queensland
Gleevec can be toxic to the heart

Subscribe to Therapy Newsletter

Enter your email address:

 Additional information about the news article
The research was funded by the National Cancer Institute. Collaborators included Yoshinobu Maeda, M.D., a former U-M research fellow; Oleg I. Krijanovski, M.D., a research fellow in internal medicine; Chen Liu, M.D., a pathologist at the University of Florida College of Medicine; and Robert Korngold, M.D., Ph.D., an immunologist and scientific director of the Hackensack University Cancer Center.
For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

Contact us

RxPG Online



    Full Text RSS

© All rights reserved by RxPG Medical Solutions Private Limited (India)