Methods for generating universal and custom MHC/HLA-compatible hematopoietic progenitor cells

Patent metadata

Field	Value
Publication number	US-11564942-B2
Application number	US-201715999463-A
Country	US
Kind code	B2
Filing date	Feb 17, 2017
Priority date	Feb 19, 2016
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

Disclosed herein are methods for generating universal MHC/HLA-compatible hematopoietic progenitor cells and methods for generating custom patient-specific MHC/HLA-compatible hematopoietic progenitor cells. Compositions comprising the universal and custom hematopoietic progenitor cells and therapeutic applications thereof are also disclosed.

First claim

What is claimed is:

1. A method of treating a pathogen infection in a subject in need thereof, said method comprising:
a) generating custom MHC/HLA-compatible hematopoietic progenitor cells for the subject, said generating comprising the steps of:
i) a contacting step, wherein the contacting step consists of contacting isolated MHC/HLA-compatible progenitor cells with a fusion protein consisting of a N-terminal cell-penetration peptide and a C-terminal a mixed-lineage leukemia (MLL) oncoprotein, the fusion protein having the sequence of SEQ ID NO: 1;
wherein said isolated progenitor cells are:
progenitor cells that give rise to subsets of mature blood cells; and isolated from bone marrow, peripheral blood, placenta, or umbilical cord of a donor subject; and

ii) a culturing step, wherein the culturing step comprises the progenitor cells of step i) with a combination of multilineage cytokines comprising stem-cell factor (SCF), Flt3 ligand, IL-3, TPO and IL-6, whereupon culturing, the progenitor cells become immortalized and exhibit commitment to neutrophil, macrophage, and/or dendritic lineage or exhibit multi-lineage blood cell differentiation potential;

b) administering the cells resulting from step a) to the subject.

2. The method of claim 1 , wherein the isolated progenitor cells are granulocyte-macrophage progenitor cells (GMP).

3. The method of claim 1 , wherein the isolated progenitor cells are mononuclear cells (MN).

Assignees

• Massachusetts Gen Hospital
• Harvard College

Inventors

• Mansour Michael K
• Sykes David B
• Scadden David T

Classifications

• C07K14/721 Primary

  Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor · CPC title

• C12N2501/125

  Stem cell factor [SCF], c-kit ligand [KL] · CPC title

• C12N2501/2303

  Interleukin-3 (IL-3) · CPC title

• C07K2319/10

  containing a tag for extracellular membrane crossing, e.g. TAT or VP22 · CPC title

• C12N5/0642 Primary

  Granulocytes, e.g. basopils, eosinophils, neutrophils, mast cells · CPC title