Cellular compositions derived from deceased donors to promote graft tolerance and manufacture and uses thereof
Inventors
Zdanowski, Michael • SUIRE, Colby • Batty, JR., D. Scott
Assignees
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Publication Number
US-11813376-B2
Publication Date
2023-11-14
Expiration Date
Abstract
The invention provides cellular compositions that contain CD34+ cells derived from bone marrow of a decease donor and CD3+ cells derived from non-bone marrow of the deceased donor. The compositions are useful to promote mixed chimerism in recipients of solid organ transplants. The invention also provides methods of making and using such compositions. In certain embodiments, the invention further provides methods of analyzing and preparing blood and blood components from a deceased donor for use in compositions of the invention to promote mixed chimerism in solid organ transplant recipients.
Core Innovation
The invention relates to a cellular product for establishing mixed chimerism in a solid organ transplant recipient. The product comprises greater than 1×10^5 CD34+ cells/kg recipient weight derived from bone marrow obtained from a deceased donor and greater than 1×10^5 CD3+ cells/kg recipient weight derived from non-bone marrow of the deceased donor.
The bone marrow used for the CD34+ cell component is contacted with an agent that mobilizes CD34+ cells. The non-bone marrow source for the CD3+ cells is selected from blood, liver, lymph nodes, spleen, or thymus.
The CD34+ cells and CD3+ cells may be HLA-matched to the solid organ transplant recipient, and the product may include a cryopreservation medium having at least one cryoprotectant selected from DMSO and dextran having a molecular weight of about 40,000 Da. The document states that the approach uses deceased-donor bone marrow combined with non-bone-marrow CD3+ cells to establish mixed chimerism in solid organ transplant recipients.
Claims Coverage
The independent claim set includes one independent claim defining a cellular product for establishing mixed chimerism in solid organ transplant recipients using specified per-recipient-weight doses from deceased donors and a CD34+ mobilization step. Dependent claims refine the mobilizing agent, the anatomical sources of bone marrow and non-bone-marrow tissues, HLA relationships, component configuration, and cryopreservation medium cryoprotectants.
Cellular product for establishing mixed chimerism in a solid organ transplant recipient
A cellular product comprising greater than 1×10^5 CD34+ cells/kg recipient weight derived from bone marrow obtained from a deceased donor, and greater than 1×10^5 CD3+ cells/kg recipient weight derived from non-bone marrow of the deceased donor.
Mobilization of deceased-donor bone marrow CD34+ cells
The obtained bone marrow is contacted with an agent that mobilizes CD34+ cells.
Deceased-donor non-bone-marrow source of CD3+ cells
CD3+ cells are derived from non-bone marrow of the deceased donor.
HLA matching of donor-derived cell components
The CD34+ cells and CD3+ cells are HLA-matched to the solid organ transplant recipient.
Cryopreservation medium with specified cryoprotectants
A cryopreservation medium includes at least one cryoprotectant selected from DMSO and dextran having a molecular weight of about 40,000 Da.
Overall, the claims coverage centers on a deceased-donor cellular product that establishes mixed chimerism in a solid organ transplant recipient using specified dose thresholds for CD34+ cells from bone marrow and CD3+ cells from non-bone marrow, with bone marrow contacted by a CD34+ mobilizing agent. Dependent refinements address donor tissue sources, HLA-matching constraints, and a cryopreservation medium including DMSO and/or specified dextran.
Stated Advantages
Documented Applications
No documented applications found
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