Treatment of epidermolysis bullosa by injection of autologous collagen vii overexpressing leukocytes

Patent metadata

Field	Value
Publication number	US-2018296600-A1
Application number	US-201615766936-A
Country	US
Kind code	A1
Filing date	Oct 27, 2016
Priority date	Oct 27, 2015
Publication date	Oct 18, 2018
Grant date	—

Abstract

Methods are provided for the cell-based delivery of collagen VII for the treatment of epidermolysis bullosa.

First claim

1 . A method for the treatment of epidermolysis bullosa (EB) in a subject, the method comprising:
administering to the subject an effective dose of a population of leukocytes that have been engineered to over-express human collagen VII (C7).

2 . The method of claim 1 , wherein the subject is a human.

3 . The method of claim 1 , wherein the subject is an immunodeficient mouse xenografted with keratinocyte/fibroblast containing skin equivalents.

4 . The method of claim 2 , wherein the human is suffering from a genetic defect in C7.

5 . The method of claim 4 , wherein the genetic defect is recessive dystrophic epidermolysis bullosa (RDEB).

6 . The method of claim 1 , wherein the leukocytes are peripheral blood mononuclear cells (PBMC).

7 . The method of claim 6 , wherein the PBMC are autologous to the subject.

8 . The method of claim 6 , wherein the PBMC are electroporated with mRNA encoding human C7.

9 . The method of claim 1 , wherein the leukocytes are B cells or plasmablasts derived therefrom.

10 . The method of claim 9 , wherein the B cells or plasmablasts derived therefrom are autologous to the subject.

11 . The method of claim 9 , wherein the B cells or plasmablasts derived therefrom are genetically modified by integration of an exogenous C7 coding sequence operably linked to a promoter active in the cell.

12 . The method of claim 11 , wherein the B cells or plasmablasts derived therefrom are further modified by integration of an exogenous prolyl-4-hydroxylase coding sequence operably linked to a promoter active in the cell.

13 . The method of claim 11 , wherein the cells are ex vivo differentiated plasmablasts.

14 . An isolated population of engineered cells for use in the methods of claim 1 .

Assignees

• Univ Leland Stanford Junior

Inventors

• Marinkovich M Peter

Classifications

• A61K35/17 Primary

  Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00) · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• C12N9/0071

  acting on paired donors with incorporation of molecular oxygen (1.14) · CPC title

• C12N5/0635

  B lymphocytes · CPC title

• C12Y114/11002

  Procollagen-proline dioxygenase (1.14.11.2), i.e. proline-hydroxylase · CPC title