Isolation and use of human lymphoid organ-derived suppressive stromal cells

Patent metadata

Field	Value
Publication number	US-2020061118-A1
Application number	US-201916538578-A
Country	US
Kind code	A1
Filing date	Aug 12, 2019
Priority date	Mar 21, 2012
Publication date	Feb 27, 2020
Grant date	—

Abstract

A method for suppressing an immune response is provided. The method involves administration of isolated lymphoid tissue-derived suppressive stromal cells (LSSC) to a subject in need of such treatment in an amount effective to suppress the immune response in the subject. The invention also involves a method to isolate LSSC by digesting lymphoid tissue fragments using a combination of an enzyme mix and agitation and then collecting the LSSC. Pharmaceutical preparations comprising LSSC are also provided.

First claim

We claim:

1 - 22 . (canceled)

23 . A pharmaceutical preparation comprising a composition of isolated lymphoid tissue-derived suppressive stromal cells (LSSCs), wherein the LSSCs are fibroblastic reticular cells (FRCs).

24 . The pharmaceutical composition of claim 23 , wherein the FRCs are isolated by treating lymphoid tissue fragments using one or more of a chemical, mechanical, and electrical cell separation process, and then by collecting the FRCs.

25 . The pharmaceutical composition of claim 24 , wherein the isolated FRCs are expanded through cell culture.

26 . The pharmaceutical composition of claim 23 , wherein the isolated FRCs are ex vivo expanded cells.

27 . The pharmaceutical composition of claim 23 , wherein the isolated FRCs are expanded by growing the collected cells until the FRCs are substantially free of non-LSSCs.

28 . The pharmaceutical composition of claim 23 , wherein the isolated FRCs co-express CD140a and PD-L2.

29 . The pharmaceutical composition of claim 23 , wherein the isolated FRCs co-express CD140a and LTBR.

30 . The pharmaceutical composition of claim 23 , wherein the isolated FRCs co-express CD140a, PD-L2, and LTBR.

31 . The pharmaceutical composition of claim 28 , wherein the isolated FRCs express at least one other lymphoid marker selected from the group consisting of PD-L1, Thy-1, MADCAM-1, MYH11, IL-7R, and ITGA7.

32 . The pharmaceutical composition of claim 23 , wherein the isolated FRCs express at least one factor selected from the group consisting of IL-6, CCL19, CCL21, and VEGF.

33 . The pharmaceutical composition of claim 23 , wherein the cells are isolated from a species selected from the group consisting of human, non-human primate, canine, feline, equine, swine, bovine, and rodent.

34 . The pharmaceutical composition of claim 23 , wherein the cells suppress T cell proliferation in vitro.

35 . The pharmaceutical composition of claim 23 , wherein the FRCs are isolated from lymph nodes, spleen, thymus, tonsils, adenoids, or Peyer's patches.

36 . The pharmaceutical composition of claim 29 , wherein the isolated FRCs express at least one other lymphoid marker selected from the group consisting of PD-L1, Thy-1, MADCAM-1, MYH11, IL-7R, and ITGA7.

37 . The pharmaceutical composition of claim 30 , wherein the isolated FRCs express at least one other lymphoid marker selected from the group consisting of PD-L1, Thy-1, MADCAM-1, MYH11, IL-7R, and ITGA7.

Assignees

• The General Hospital Corp D/B/A Massachusettes General Hospital
• Dana Farber Cancer Inst Inc

Inventors

• Fletcher Anne
• Turley Shannon J
• Parekkadan Biju

Classifications

• A61P37/06

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

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title