Immunologically privileged cells and uses thereof

Abstract

The invention is directed to immunologically privileged cells, e.g., autologous, allogeneic, and xenogeneic intermediate lobe pituitary cells, for delivering polypeptides, e.g., insulin, to a subject, and to methods of using the same.

Description

[0001] This application is a continuation of U.S. Ser. No. 09 / 770,601, filed Jan. 26, 2001, now U.S. Pat. No. N,NNN,NNN which is a division of U.S. Ser. No. 09 / 127,296, filed Jul. 30, 1998, now abandoned, and claims the benefit of U.S. Provisional Application Ser. No. 60 / 054,730, filed Aug. 5, 1997. The contents of all of the prior applications are incorporated herein by reference.GOVERNMENT RIGHTS [0002] This invention was made with government support under grant numbers DK 53281 and DK 53087 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION [0003] The invention relates to immuno privileged cells and the use thereof in tissue transplant and cell-based therapies. [0004] Insulin dependent diabetes mellitus (IDDM) in humans and in non-obese diabetic (NOD) mice is an immune-mediated disorder in which mononuclear cells invade the pancreatic islets of Langerhans (insulitis) and effect the selective destruction of ...

AI Technical Summary

Benefits of technology

The patent describes a method of delivering polypeptides, such as insulin, to a subject using immunologically privileged cells. These cells are resistant to damage and autoimmune attack, making them ideal for delivering therapeutic proteins. The cells are implanted systemically in the subject and can be introduced into humans or animals for veterinary use. The method can also involve gene therapy techniques to transfect the cells with nucleotides that promote the expression of insulin or other therapeutic proteins. The technical effects of this invention include improved delivery of therapeutic proteins to the subject and reduced risk of damage or destruction of the cells.

Problems solved by technology

However, current insulin treatment regimens are still suboptimal for blood glucose control and patients with IDDM are at significant risk for the development of serious long-term complications such as blindness and kidney disease.

Although progress is being made in the field of allogeneic islet transplantation as an alternative approach to the treatment of IDDM, the clinical applicability of this approach has been severely limited by the scarce supply of available islets and the rapid and aggressive recurrence of autoimmune disease in transplanted islet grafts, which occurs despite treatment with systemic immunotherapy (Tyden et al., NEJM, 1996).

A major limitation of using transfected anterior pituitary cells for insulin gene delivery is that their major endogenous secretory product is ACTH, and, thus, implantation of these cells into diabetic recipients can result in a severe Cushings-like hypercortisolemic syndrome (BeltrandelRio, H., Schnedl, W. J., Ferber, S.

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