This invention includes novel methods for creating and isolating regulatory T cells (Tregs) for use in adoptive immunotherapy.
Adoptive immunotherapy is a patient-specific treatment for a range of diseases and for facilitating transplantation procedures. It involves the extraction, processing, and replacement of a patient's immune cells, with the goal of diminishing the adverse effects of resident immune cells. Regulatory T cells (Tregs) are capable of achieving this by reducing or eliminating the attacking activities of the offending cells. Thus, there is significant interest in developing methods of obtaining or creating Tregs from peripheral blood of patients. The existing process of Treg isolation and expansion in culture sometimes results in reduced functioning of the cells. The present invention provides a new way of generating these cells by inducing another type of T cell (naive T cells) to differentiate into Tregs through a process of stimulation in culture.
The method is intended to be used in adoptive immunotherapy as a treatment for autoimmune diseases, allergies and inflammatory diseases, and for facilitating organ, tissue, bone marrow, and stem cell transplantation.
Adoptive immunotherapy is a patient-specific treatment, meaning that the immune cells are taken from and replaced into the same patient. In the present invention, naive T cells are isolated from the patient's blood. Using a selective treatment of TCR (CD3) stimulation along with ICAM-1 ("CD54") as a co-stimulatory signal, these cells are induced to differentiate into regulatory T cells within 7 to 10 days. The cells may then be further proliferated before being replaced into the patient to target the specific tissue where damage is being induced (for example, the joints in rheumatoid arthritis or the pancreas in insulin-dependent diabetes).
Successful immunotherapy can be aided by increasing the quantity of the regulatory T cells. The methods of the present invention provide a purified composition with very high numbers of regulatory T cells.
One problem with expansion in culture of existing Tregs isolated from peripheral blood is that they do not expand well and sometimes do not function well after expansion. The present technology avoids this problem because it creates Tregs by stimulating another type of T cell in culture to become a Treg, rather than stimulating existing Tregs to divide. Data suggest that the method of stimulation may also allow influence over the ability of developing T cells to home to different tissues.
Adoptive immunotherapy is also used in the treatment of cancer and virus infections.