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Methods and compositions for mobilizing stem cells

a technology of stem cells and compositions, applied in drug compositions, plant/algae/fungi/lichens, immune disorders, etc., can solve the problems of critical unmet needs, and achieve the effect of assessing the ability of test agents

Inactive Publication Date: 2020-08-27
PRESIDENT & FELLOWS OF HARVARD COLLEGE +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method for mobilizing hematopoietic stem cells and progenitor cells in a person's body. This can be done by collecting the stem cells from the person's peripheral blood through a process called apheresis. The method involves using a combination of two or more agents to deplete stem cells in the person's body and make them available for transplantation. The method can be performed on the same day as the stem cell collection and can lead to a rapid and effective mobilization of stem cells from the person's body. The patent also describes a composition that can be used to achieve this method. Overall, the patent provides a technical solution for efficiently and safely collecting and engrafting stem cells for therapeutic purposes.

Problems solved by technology

Despite its common use, there remain critical unmet needs to improve transplant efficiency and patient access, as only a fraction of patients who could benefit from an HSC transplant actually receive one.

Method used

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  • Methods and compositions for mobilizing stem cells
  • Methods and compositions for mobilizing stem cells
  • Methods and compositions for mobilizing stem cells

Examples

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example 1

the Toxicity of Conditioning to Lower the Barrier for Achieving a HSC Transplant Therapy for HIV / AIDS

[0321]Hematopoietic stem cell (HSC) transplantation is the one known basis for apparent cure of HIV. The ‘Berlin patient’ in whom an allogeneic CCR5− / − hematopoietic graft after intensive chemotherapy provided a durable state of undetectable HIV, provides strong rationale for a stem cell based approach.1 Recently, two additional patients treated with allogeneic transplantation were reported to have undectable HIV viral load at 8 and 17 months post-transplant. (Abstract THAA0101 XIX International AIDS Conference, Washington, D.C.; Jul. 22-27, 2012) In addition, genetically modified HSC to enhance HIV resistance have been tested in clinical trials.2 (and unreported Systemix sponsored multi-center trial, DTS as investigator) Multiple efforts to leverage emerging gene modification strategies such as TALENs and zinc-finger nucleases are focused on creating HIV resistant autologous HSC tha...

example 2

iche Vacancy without Niche Toxicity Through Manipulation of CXCR2 and CXCR4

[0326]Preclinical data suggests that CXCR2 agonists may be superior to current standard of care both in terms of the kinetics of action and the quality of cells that get mobilized. The goal of this project is to test existing GSK CXCR2 agonists, Gro-beta in combination with the CXCR4 inhibitor Mozobil®, and compare outcomes to current standard of care for mobilization, engraftment, and as non-toxic conditioning regimens. Animals will be treated with various combinations of G-CSF, Plerixafor (e.g., Mozobil®), Gro-beta or other mobilizing agents and tested for their ability to induce HSC mobilization. Cells mobilized will be analyzed for their in vitro & in vivo functional capacities and ability to enhance survival and hematopoietic recovery in irradiated mice. Cells will be characterized via functional assays, immunohistochemistry and transcriptomics to help define variations in mobilized stem cell populations...

example 3

iche Vacancy without Niche Toxicity Through Manipulation of CXCR2 and Recently Defined Heparan Sulfate Proteoglycan Interactions Between HSC and the Bone Marrow Niche

[0333]Niche retention of HSPC is partially maintained by the interaction of SDF-1 with its cognate receptor CXCR4 on HSPC. Clinically, the CXCR4 antagonist AMD3100 is FDA approved for use in combination with G-CSF to enhance egress of HSPC from the bone marrow to the periphery for harvesting via apheresis and subsequent transplantation. While this combination clearly vacates the bone marrow niche, G-CSF causes significant attenuation of stromal niche cells.18 This is of little consequence when the goal is simply stem cell harvesting, but it is problematic when considering vacating the niche to enable competing cells to engraft in the setting of low toxicity conditioning. This may be why G-CSF has been unsuccessful in this context; it reduces the supportive capacity of the niche for infused and endogenous cells. Therefor...

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Abstract

The present invention relates to methods and compositions for mobilizing hematopoietic stem cells and / or progenitor cells, and related methods of conditioning for engraftment of transplanted hematopoietic stem cells and / or progenitor cells, and methods of treating diseases requiring hematopoietic stem cell and / or progenitor cell transplantation.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 14 / 771,280, filed Aug. 28, 2015, which is a national stage filing under 35 U.S.C. 371 of International Application No. PCT / US2014 / 19596, filed Feb. 28, 2014, which claims the benefit of U.S. Provisional Application No. 61 / 770,533, filed Feb. 28, 2013, U.S. Provisional Application No. 61 / 828,568, filed May 29, 2013, and U.S. Provisional Application No. 61 / 904,768, filed Nov. 15, 2013. The entire teachings of the above applications are incorporated herein by reference.GOVERNMENT SUPPORT[0002]This invention was made with government support under HL044851, HL97794 and DK50234 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Hematopoietic stem cell (HSC) transplantation is a common life-saving medical procedure used to treat and cure approximately 60,000 patients per year globally. Despite its common ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/19A61K45/06A61K35/28A61K31/395A61K31/727A61K38/20A61K38/17G01N33/50
CPCA61K38/195A61K45/06A61K35/28A61K36/00A61K31/727G01N33/5073A61K38/193A61K2035/124A61K31/395A61K38/1703A61K38/202A61P1/04A61P13/12A61P17/00A61P19/02A61P25/00A61P29/00A61P31/18A61P35/00A61P35/02A61P37/02A61P43/00A61P7/00A61P7/06A61K2300/00A61K2039/505C12N15/115C12N5/0662C12N2310/16C12N15/1136A61K39/3955C12N2310/11
Inventor SCADDEN, DAVID T.SAEZ, BORJAFERRARO, FRANCESCAHOGGATT, JONATHAN
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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