Use of apoptotic cells ex vivo to generate regulatory T cells

Patent metadata

Field	Value
Publication number	US-10138464-B2
Application number	US-201514863274-A
Country	US
Kind code	B2
Filing date	Sep 23, 2015
Priority date	Nov 2, 2005
Publication date	Nov 27, 2018
Grant date	Nov 27, 2018

Abstract

Many cell types in the body can remove apoptotic and cellular debris from tissues; however, the professional phagocyte, or antigen presenting cell (“APC”), has a high capacity to do so. The recognition of apoptotic cells (“ACs”) occurs via a series of evolutionarily-conserved, AC associated molecular-pattern receptors (“ACAMPRs”) on APCs that recognize and bind corresponding apoptotic-cell-associated molecular patterns (“ACAMPs”). These receptors recognize ligands such as phosphotidyl serine and oxidized lipids found on apoptotic cells. Savill et al. (2002); and Gregory et al. (2004).

First claim

The invention claimed is:

1. A method of generating T cells with regulatory activity (T regs), the method comprising incubating CD4+ leukocytes with autologous apoptotic peripheral blood mononuclear cells (ACs) and IL-10.

2. The method according to claim 1 , wherein the incubation is at about a 1:10 to about a 10:1 ratio CD4+:ACs.

3. The method according to claim 2 wherein the incubation is at about a 2:1 to about a 1:2 ratio CD4+:ACs.

4. The method according to claim 1 wherein the ACs are obtained by an apoptosis-inducing treatment.

5. The method according to claim 4 wherein the apoptosis-inducing treatment is an ECP procedure that employs a photoactivatable compound together with light of a wavelength that activates the photoactivable compound.

6. The method according to claim 5 wherein the photoactivable compound is a psoralen and the light is UVA.

7. The method according to claim 6 wherein the psoralen is 8-MOP.

8. The method according to claim 1 , wherein the IL-10 is present at a concentration of about 1 ng/ml to about 100 ng/ml.

9. The method according to claim 8 wherein the IL-10 is present at a concentration of about 20 ng/ml.

10. The method according to claim 1 wherein the incubation is for about 1 to about 14 days.

11. The method according to claim 10 wherein the incubation is for about 8 days.

Assignees

• Mallinckrodt Hospital Products Ip Ltd

Inventors

• Peritt David
• Campbell Kim
• Krutsick Amy

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K31/59

  Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems · CPC title