Compositions for establishing mixed chimerism and methods of manufacture thereof
Inventors
Assignees
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Publication Number
US-11701392-B2
Publication Date
2023-07-18
Expiration Date
Abstract
The invention provides compositions for establishing mixed chimerism in a subject. The compositions include CD34+ cells that have been column-purified from an apheresis product and CD3+ cells from an apheresis product that have not been purified through a column. The invention also provides methods of making and using such compositions.
Core Innovation
The invention relates to a method of manufacturing a cellular product for establishing mixed chimerism in a solid organ transplant recipient. The method receives an apheresis product containing CD34+ cells and CD3+ cells from a solid organ transplant donor, and divides the apheresis product into a first portion and a second portion. The first portion is purified to obtain an enriched amount of CD34+ cells.
A cellular product is created by introducing from the second portion to the enriched amount of CD34+ cells the obtained CD3+ cells in an amount greater than 1×10^5 CD3+ cells/kg recipient weight. Donor blood circulating factors are also introduced from the blood of the donor to the enriched amount of CD34+ cells, thereby creating a cellular product for establishing mixed chimerism.
The solid organ transplant context includes mixed chimerism as a means for immune tolerance in the solid organ transplant recipient, with attention to avoiding graft rejection and graft-versus-host disease (GVHD) associated with chimerism approaches. The manufacturing concept is based on using an apheresis-derived first portion enriched for CD34+ cells while retaining donor-derived circulating factors associated with the second portion, rather than relying on purified column effluent.
Claims Coverage
The document provides one independent claim directed to a manufacturing method for a cellular product to establish mixed chimerism in a solid organ transplant recipient. The independent claim is centered on dividing an apheresis product, purifying a first portion to enrich CD34+ cells, and combining that enriched fraction with CD3+ cells at a stated dose threshold and donor blood circulating factors to create the cellular product for establishing mixed chimerism.
Manufacturing a cellular product from split apheresis portions for mixed chimerism
Receiving an apheresis product containing CD34+ cells and CD3+ cells from a solid organ transplant donor, dividing the apheresis product into a first portion and a second portion, and purifying the first portion to obtain an enriched amount of CD34+ cells.
Combining enriched CD34+ with CD3+ dose and donor blood circulating factors
Introducing from the second portion to the enriched amount of CD34+ cells the obtained CD3+ cells in an amount greater than 1×10^5 CD3+ cells/kg recipient weight and circulating factors from blood of the donor to thereby create a cellular product for establishing mixed chimerism.
Column purifying the first portion to enrich CD34+ cells
Purifying the first portion to obtain an enriched amount of CD34+ cells.
Using an expanded CD3+ cell dose threshold per kg recipient weight
The cellular product includes an amount greater than 1×10^5 CD3+ cells per kilogram of recipient weight.
Not column purifying CD3+ cells and donor circulating factors from the second portion
Introducing from the second portion to the enriched amount of CD34+ cells the CD3+ cells and circulating factors in a manner that specifies that the CD3+ cells and the circulating factors are not column purified from the second portion.
Selecting donor HLA type matched to recipient HLA type
Using a donor whose Human Leukocyte Antigen (HLA) type is matched to the recipient's HLA type.
Across the independent claim and its dependent refinements described in the provided material, the core claim coverage focuses on split-processing an apheresis product, column purification of a first portion to enrich CD34+ cells, and creating the mixed-chimerism cellular product by introducing second-portion CD3+ cells above a specified per-kg threshold along with donor circulating factors, together with optional refinements including non-column processing of the second-portion components and HLA-matched donor selection.
Stated Advantages
Mixed chimerism as a means for immune tolerance in the solid organ transplant recipient.
Avoiding graft rejection and graft-versus-host disease (GVHD) associated with chimerism approaches.
Documented Applications
Establishing mixed chimerism in a solid organ transplant recipient.
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