Methods of analysis of blood from deceased donors
Inventors
Zdanowski, Michael • SUIRE, Colby • Batty, JR., D. Scott
Assignees
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Publication Number
US-11435350-B2
Publication Date
2022-09-06
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 disclosed invention relates to assessing blood derived from a deceased donor to determine suitability for manufacturing a product comprising mature T cells and hematopoietic stem and progenitor cells (HSPCs) for administration to a living recipient. The approach focuses on analyzing mature T cells and HSPCs in the deceased-donor blood by comparing parameter values against parameter values from one or more healthy living donors of blood or blood-derived products.
For the mature T cells, the method analyzes a parameter that is an indicator of T cell activation, T cell proliferation, T cell viability, T cell exhaustion, T cell anergy, or T cell apoptosis. For the HSPCs, the method analyzes a parameter that is an indicator of HSPC apoptosis, HSPC proliferation, or HSPC viability.
Suitability is determined by determining that the values of the parameters of the deceased-donor blood are comparable to the values of the parameters of the blood from the one or more healthy living donors. When the values are comparable, material from the analyzed deceased-donor blood is used in manufacture of the product comprising mature T cells and HSPCs for administration to a living recipient. The non-cellular component-based assessment of HSPC apoptosis, including cytokines and chemokines, is explicitly described as an indicator basis for the HSPC apoptosis parameter.
Claims Coverage
The document provides two independent claims, for blood derived from a deceased donor in general and specifically for peripheral blood. Each independent claim includes a suitability decision based on comparing deceased-donor indicator parameter values to one or more healthy living donor indicator parameter values, covering mature T cell condition indicators and HSPC condition indicators, followed by manufacture using material from the analyzed deceased-donor blood.
Deceased-donor blood suitability assessment by parameter comparison
Obtaining blood derived from a deceased donor; analyzing mature T cells and HSPCs by comparing values of parameters that are indicators of T cell activation, T cell proliferation, T cell viability, T cell exhaustion, T cell anergy, or T cell apoptosis, and indicators of HSPC apoptosis, HSPC proliferation, or HSPC viability; determining the blood is suitable if the values are comparable to values from one or more healthy living donors; and using material from the analyzed blood derived from the deceased donor in manufacture of a product comprising mature T cells and HSPCs to administer to a living recipient.
Peripheral blood suitability assessment for manufacture of mature T cells and HSPCs
Obtaining peripheral blood from a deceased donor; analyzing mature T cells of the peripheral blood by comparing a value of a parameter that is an indicator of T cell activation, T cell proliferation, T cell viability, T cell exhaustion, T cell anergy, or T cell apoptosis to a value of the parameter of blood obtained from one or more healthy living donors; analyzing HSPCs of the peripheral blood by comparing a value of a parameter that is an indicator of HSPC apoptosis, HSPC proliferation, or HSPC viability to a value of the parameter of blood obtained from one or more healthy living donors; determining the peripheral blood is suitable if the values are comparable; and using material from the analyzed peripheral blood obtained from the deceased donor in the manufacture of the product comprising mature T cells and HSPCs to administer to a living recipient.
Across both independent claims, the inventive concept is that deceased-donor blood, including peripheral blood, is judged suitable for manufacturing a mature T cell/HSPC product by comparing specific indicator parameter values for mature T cell condition and HSPC condition against comparable values from healthy living donors, and then using material from the analyzed deceased-donor blood when the values are comparable.
Stated Advantages
Enables determining suitability of deceased-donor blood for manufacture of a product comprising mature T cells and HSPCs when indicator parameter values are comparable to one or more healthy living donors.
Documented Applications
Assessing whether deceased-donor derived blood, including peripheral blood, is suitable for use in manufacture of a product comprising mature T cells and HSPCs to administer to a living recipient for solid organ transplant tolerance via inducing mixed chimerism.
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