Cellular compositions derived from prior organ donors and methods of manufacture and use thereof
Inventors
Assignees
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Publication Number
US-11819521-B2
Publication Date
2023-11-21
Expiration Date
Abstract
The invention provides methods of making and using compositions for establishing mixed chimerism in a subject that include CD34+ cells and CD3+ cells derived from an apheresis product obtained from a subject that has previously donated a solid organ.
Core Innovation
The invention relates to cellular compositions and associated manufacturing and use for establishing mixed chimerism in a recipient of a solid organ transplant. A cellular product is administered after the recipient has already undergone a solid organ transplant procedure, and the cellular product is derived from at least one apheresis product obtained from a subject that has donated the transplanted solid organ.
The apheresis product is obtained from the subject at least one day after the subject has donated the solid organ, and the cellular product includes CD34+ cells and CD3+ cells. The document describes HLA-matched or HLA-mismatched arrangements across specified HLA genes and allele counts, and the cellular product can be cryopreserved with a cryoprotectant selected from dimethyl sulfoxide (DMSO) and dextran having an average molecular weight of 40,000 Da.
The document also describes manufacturing in which a first portion of the at least one apheresis product is purified or enriched for CD34+ while a second portion comprising CD3+ is retained and used, including combining enriched CD34+ with the retained CD3+ cells. The invention states quantitative cell-dose targets per kilogram recipient weight, including greater than 5×10^5 CD34+ cells/kg and greater than 1×10^5 CD3+ cells/kg, to support the establishment of mixed chimerism.
Claims Coverage
The independent claim family covers one main inventive concept for establishing mixed chimerism in a solid organ transplant recipient, supported by six inventive features.
Post-transplant administration of donor-derived cellular product for mixed chimerism
Administering at least one cellular product for establishing mixed chimerism to a recipient of a solid organ transplant after the recipient has already undergone a solid organ transplant procedure, wherein the cellular product is derived from at least one apheresis product obtained from a subject that has donated the transplanted solid organ.
Apheresis obtained after donation with defined minimum post-donation timing
The apheresis product is obtained from the subject at least one day after the subject has donated the solid organ.
Quantitative CD34+ and CD3+ cell-dose targets per kg recipient weight
The cellular product comprises greater than 5×10^5 CD34+ cells/kg recipient weight and greater than 1×10^5 CD3+ cells/kg recipient weight.
Cryopreserved cellular product with defined cryoprotectant selection
The cellular product comprises at least one cryoprotectant.
Cryoprotectant selected from DMSO or 40,000 Da dextran
The cryoprotectant is selected from dimethyl sulfoxide (DMSO) and dextran having an average molecular weight of 40,000 Da.
CD34+ enrichment with retained CD3+ fraction from the same apheresis product
Manufacturing comprises purifying a first portion of the at least one apheresis product to obtain an enriched amount of CD34+ cells and retaining a second portion comprising CD3+ cells.
Overall, the claims focus on establishing mixed chimerism by post-transplant administration of a donor-derived cellular product obtained from an apheresis product collected after donation, with defined CD34+ and CD3+ dose thresholds, optional cryopreservation with specified cryoprotectants, and a manufacturing approach separating enriched CD34+ from a retained CD3+ fraction.
Stated Advantages
Tolerance without lifelong immunosuppression.
Documented Applications
Establishing mixed chimerism in solid organ transplant recipients using CD34+ and CD3+ cellular products derived from donor apheresis material collected after organ donation.
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