Immune modulation to improve stem cell engraftment

Funding Type: 
Transplantation Immunology
Grant Number: 
RM1-01716
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
Stem cells can give rise to many different types of cells and tissues in our body. Therefore, stem cell transplantation has been considered as a promising alternative to current therapeutic approaches in treating cancer and autoimmune diseases. The premise upon which stem cell treatment is based is that replenishment of diseased or destroyed tissues with cells derived from transplanted stem cells would prevent the progression of or potentially cure disease. However, similar to what occurs in organ transplantation, most if not all available sources for stem cells are from individuals of distinct genetic background. Consequently, the patient receiving stem cell transplantation typically develops a harmful immune response that attacks and destroys the transplanted stem cells or their derivatives. The development of novel methods to overcome such harmful immune responses becomes necessary before a successful stem cell based therapy for diseases, such as cancer or autoimmune diseases, can be applied clinically. Recent developments in research suggest that development of cancer or autoimmune diseases could be due to an imbalance in the immune system. As such, (re)establishing the balance in the immune system may hold great promise for prevention, intervention and cure of disease. Important findings in immunology in the past few years showed that a specialized population of immune cells, called regulatory T cells, functions by regulating other immune cells and, in turn, the body’s immune response. We hypothesize that these cells can potentially be used to modulate both immunity and autoimmunity, and consequently the direction of the body’s immune responses. We and others have shown that regulatory T cells may inhibit autoimmune diseases such as type 1 diabetes and participate in the regulation of tumor development. The purpose of our proposed studies is to determine whether regulatory T cells can also be used to overcome the immunological barriers imposed by patients receiving treatment, and re-balance the immune system in order to provide an environment that is much more suitable for stem cell grafts. It is expected that, for cell replacement therapy, regulatory T cells can induce immune tolerance to promote acceptance of stem cells allowing their growth and replacement of damaged cells in patients and leading to disease cure.
Statement of Benefit to California: 
More than 1 million Californians have a history of cancer, and an estimated nearly 150,000 new cases will be diagnosed in 2010. In addition, autoimmune diseases such as type 1 diabetes and multiple sclerosis, also affect hundreds of thousands of Californians every year. These life-threatening diseases result in deteriorating health conditions and have devastating effects in terms of patient quality of life. While the heavy emotional, physical and financial impact of these diseases is felt by patients and their families, a significant economic burden is also felt by the State, as treatment and care of these patients costs California billions of dollars every year. Additional losses are incurred by the private and public sectors resulting from reduced worker productivity, absence from work and loss of future earnings. The rising cost of medical care is an additional factor underscoring the critical need to develop novel therapies to prevent and treat patients with on-going autoimmune disease. Stem cell transplantation is a promising alternative to current therapeutic approaches in treating cancer and autoimmune disease patients, due to the potential for stem cells to develop into many different types of cells and tissues in the body. Although promising, engraftment of stem cells, as well as cells or tissues derived from stem cells, still suffer from immune or autoimmune attacks and subsequent destruction from the patient’s own immune system, resulting in potential treatment failure or the need for extended patient care. Recent developments in research have suggested that development of cancer or autoimmune diseases could be due to an imbalance in the immune system. It is likely that (re)establishing the balance of the immune system may hold great promise in both prevention and intervention of the diseases. The proposed studies using T cells with potent regulatory function are expected to achieve this goal by inducing active immune tolerance in patients. Should our proposed studies be successful, our results will provide a solid base to facilitate rapid translation of our findings from laboratory to clinics, overcoming the immunological barriers imposed by host patients, with significant medical and economic benefits to Californians in terms of effective treatment of cancer and autoimmune diseases.

© 2013 California Institute for Regenerative Medicine