Apoptosis-mimicking synthetic entities and use thereof in medical treatment

#This invention relates to synthetic and semi-synthetic compositions having biochemical activity, and to the uses thereof in the treatment and/or prophylaxis of various disorders in mammalian patients. More particularly, it relates to preparation and use of synthetic and semi-synthetic bodies which can mimic the process of cell apoptosis after introduction into the body of a patient, to produce beneficial effects.

#The following documents are cited herein:

#1. Kerr, J. F. R., Wyllie A. H., Currie, A. R. (1992), “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.” British Journal of Cancer 26: 239-257;

#FIG. 1 shows net ear swelling (microns) in control and treated mice using the murine contact hypersensitivity (CHS) model.

#FIG. 2 shows net ear swelling in control and treated mice in the CHS model where mice were treated with PS liposomes where the amount of PS in the liposome was varied.

#FIG. 3 shows the change in ear swelling in control and treated mice where mice were treated with varying numbers of liposomes using the CHS model.

#According to the present invention, synthetic and semi-synthetic bodies which have the property of mimicking in vivo apoptotic cells and/or apoptotic bodies in that they are taken up by cells of the patient's immune system with accompanying beneficial effects such as inhibition of pro-inflammatory cytokines in vivo and/or promotion of anti-inflammatory cytokines are administered to patients. These synthetic and semi-synthetic bodies are three dimensional bodies having shapes and dimensions ranging from those resembling mammalian cells to shapes and dimensions approximating to apoptotic bodies produced by apoptosis of mammalian cells (typically but not exclusively spheroidal, cylindrical, ellipsoidal including oblate and prolate spheroidal, serpentine, reniform, etc., and from about 50 nanometers to about 500 microns in diameter), and having phosphatidyl serine (PS) molecules on the surface thereof. Such bodies are hereinafter referred to as “PS-carrying bodies”.

#The term “synthetic or semi-synthetic PS-carrying bodies” refers to liposomes containing PS as well as up to 50% non-PS components of the liposomes. The term “non-liposomal synthetic bodies” refers PS-carrying bodies that are not liposomes.

#As noted above, exposed PS on the membrane of a cell is known to play a key role in the clearance of apoptotic lymphocytes by macrophages. A receptor for PS is present on macrophages. A “phosphatidylserine receptor” or “PS receptor” is a receptor on an antigen presenting cell (APC), such as a macrophage, whose activity is blocked by soluble phosphatidylserine, either monomeric or oligomeric. It is contemplated that the PS receptor may also be present on other APCs, such as dendritic cells and B cells. It is understood that PS is a ligand of the PS receptor.