Novel approach for depletion of TCRab+ and CD45RA+ cells from apheresis products products using the CliniMACS Prodigy (original) (raw)

DLI resulted in dominant donor T & B cell chimerism (Figure 1A,B) unlike other subsets (Figure 1C,D). BAL values exhibited different kinetics (Figure 1). T & B cells, TCR/BCR repertoires, & TREC exceeded pre-BMT values by 3-6m (Figure 2A, B). BK virus specific T cells cleared viremia(Figure 2C). Mild skin GVHD post-DLI cleared in 2w with <1 mg/kg prednisone. Serial lung biopsies have been negative for rejection at last f/up (Nov17; 5m off ISD). At 18m post-BMT (2m post-ISD withdrawal), circulating donor T cells were unresponsive to host DC while responded to 3 rd party APC (Figure 3), fulfilling a critical tenet of tolerance. Tolerance towards host APC was Treg & Tr1 independent(Figure 3). Case 2: 38y/o woman with CVID on ECMO underwent BOLT. She had 3 episodes of lung rejection before becoming eligible for BMT (1/8 match) 14 months later(Nov17) (3E6 CD34+cells/kg, 2E3 CD3+cells/kg infused). She engrafted by D+12 with 95% whole blood chimerism but T cells of host origin that is treated with DLI. Case 1 is the first in human to demonstrate 1) durable engraftment, 2) immune competence, and 3) acquisition of tolerance from deceased donor VB marrow 4) matched only at a single class I MHC allele, providing proof of principle, that is currently also tested in adults.