Disease therapy using dying or dead cells

Abstract

A method of treating a disease characterized by a pathological immune response in a subject in need thereof is disclosed. The method comprises administering to the subject a therapeutically effective amount of a cell preparation which comprises dying or dead leukocytes, the dying or dead leukocytes being capable of suppressing the pathological immune response, thereby treating the disease in the subject.

Description

[0001] This is a continuation-in-part of U.S. patent application Ser. No. 10 / 470,536, filed Jul. 8, 2004, which is a National Phase of PCT Patent Application No. PCT / IL02 / 00089, filed Jan. 31, 2002, which claims the benefit of priority of U.S. Provisional Patent Application No. 60 / 265,127, filed Jan. 31, 2001, the contents of which are hereby incorporated by reference.FIELD AND BACKGROUND OF THE INVENTION [0002] The present invention relates to methods of using dying cells for treating diseases characterized by pathological immune responses, and to devices for preparing such dying cells. More particularly, the present invention relates to methods of using apoptotic leukocytes for treating diseases characterized by pathological immune responses, such as autoimmune diseases and transplantation related diseases, and to devices for preparing such apoptotic leukocytes. [0003] Diseases characterized by pathological immune responses include a large number of diseases which are associated w...

AI Technical Summary

Benefits of technology

[0052] The present invention successfully addresses the shortcomings of the presently known configurations by providing a method of treating with improved safety and effectiveness diseases associated with pathological immune responses, such as autoimmune diseases and GVHD, by administration of dying or dead leukocytes, by providing a device for generating such leukocytes, and by providing a device for practicing such methods.

Problems solved by technology

Diseases characterized by pathological immune responses include a large number of diseases which are associated with significant mortality and morbidity, and for which no satisfactory / optimal treatments are available.

Were it not for the cellular debris-removing cells of the immune system, typically macrophages, tissue and organ growth would be impossible due to a lack for space.

However, in the absence of infection and conditioned media, immature dendritic cells do not mature following uptake of apoptotic cells and as a consequence are less able to efficiently present acquired antigens.

When the immune system is deficient in recognition between self- and non-self-antigens, the result is a: state of disease, this may result in the immune system attacking one or more specific self molecules or cells leading to tissue and organ damage, resulting in autoimmune disease.

This armory has the potential to destroy healthy cells and tissues because many of the effector molecules, such as pro-inflammatory cytokines, act in a non-antigen-specific manner and also because certain pathogen-specific receptors, such as B-cell receptors (BCRs) and T-cell receptors (TCRs) may cross-react with host antigens.

Immune responses to pathogens therefore pose a potential danger to the host and immunopathology occurs with many types of infection.

However disregulation of this process may represent a mechanism of escape from immune surveillance against infections and tumors and, if inefficient, it may support persistent inflammation and autoimmunity [16, 17].

Another issue that remains unclear is the role of apoptotic cell-derived antigens in cross-priming of immune responses.

While such drug-induced immunosuppression has resulted, for example, in improvement of the 5-year survival rate of SLE patients in the last three decades, it is far from being an ideal treatment since no cure is achieved, since such treatment is associated with very serious side-effects, including general immune suppression, leading to high rates of morbidity, and is the primary cause of premature mortality.

However, the toxicity and efficacy of such treatments is suboptimal, being potentially associated, for example, with general immune suppression similarly to the above-mentioned immunosuppressive drugs.

Suchan approach, however, suffers from various drawbacks, including requirement for administration of allogeneic leukocytes, which inherently are associated with risk of GVHD as well as of their own rejection, suboptimal efficacy, failure to demonstrate adequate safety with respect to potential for inflammatory side-effects, and / or of never having been attempted in human patients, and hence of never having demonstrated any therapeutic efficacy in human patients.

Prior art approaches involving apheresis, however, are often suboptimally effective, and may be associated with undesired side-effects of unknown origin, such as inflammatory side-effects (refer, for example, to: Siami G A. et al., 1997.

Risks and safety practices in hemapheresis procedures.

Thus, all prior art approaches have failed to provide an adequate solution for: using dying leukocytes for treatment of diseases characterized by pathological immune responses.

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