Background The success of autologous CAR-T cell therapies has revolutionized and accelerated development in the cell therapy field. However, the requirement for patient-specific starting material for these therapies remains an impediment to establishing availability for all patients who could benefit, highlighting the need for a highly characterized normal donor pool to generate allogeneic cell therapy material.
Methods We have established a network of >2800 normal donors that have been genotyped at the HLA loci (6 digits) and stratified by reactivity to common human viruses, such as cytomegalovirus (CMV) and Epstein Barr Virus (EBV). Furthermore, cell collections from 35 randomly selected donors have been screened by flow cytometry for major immune cell subsets, including T cells, B cells, NK cells, and monocytes. The T cell compartment was further characterized by expression of activation markers (CD25, PD1, CD69) and proliferative capacity in response to anti-CD3/CD28 stimulation.
Conclusions There was substantial variability (%CV 14.52%-50.58%, see table 1) in the percentage of each immune cell population across the donor pool, which would have effects on the relative success of downstream cell manufacturing. We are evaluating additional donors to identify specific sources of variability. Collectively, these data highlight the need for in-depth genotypic and phenotypic characterization of donor populations to ensure that the most robust material is selected for each type of cell therapy manufacturing.
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