Functional characterization of alloreactive T cells identifies CD25 and CD71 as optimal targets for a clinically applicable allodepletion strategy.

摘要: Immunotherapy with allodepleted donor T cells (ADTs) improves immunity after cell-depleted stem cell transplantation, but infection/relapse remain problematic. To refine this approach, we characterized the expression of surface markers/cytokines on proliferating alloreactive (ATs). CD25 was expressed 83% carboxyfluorescein diacetate succinimidyl ester(dim) ATs, confirming as an excellent target for allodepletion. Seventy percent CD25(-) ATs CD71 (transferrin receptor), identifying a novel marker to persisting depletion. Comparison residual alloreactivity combined CD25/71 versus immunomagnetic depletion showed enhanced host in both secondary (2 degrees) mixed lymphocyte reactions (P < .01) and interferon-gamma enzyme-linked immunospot assays .05) no effect third-party responses. In pentamer/interferon-gamma assays, antiviral responses cytomegalovirus, Epstein-Barr virus, adenovirus were preserved ADTs can be redirected recognize leukemic targets through lentiviral transfer chimeric anti-CD19 zeta T-cell receptor. Finally, have established conditions clinically applicable allodepletion under European Union Good Manufacturing Practice conditions, resulting highly effective, reproducible, selective (median 2 degrees reaction 0.39% vs response 62%, n = 5). This strategy enables further clinical studies adoptive immunotherapy larger doses enhance immune reconstitution transplantation. (Blood. 2010; 115: 396-407)