T-lymphocyte recovery and function after cord blood transplantation

Abstract

The Szabolcs laboratory is focused on understanding the biology of donor-derived cellular immunity in recipients of allogeneic hematopoietic cell transplantation that can be translated into new immunotherapy strategies. To this end, we are focused on developing novel laboratory approaches to analyze and augment immune recovery for high risk patient cohorts without increasing graft-versus-host disease. Much of our work has focused on unrelated cord blood transplantation as the dominant clinical scenario and laboratory model. Our overarching goal is to minimize transplant-related mortality and morbidity and render HLA-mismatched unrelated cord blood transplant, a widely accepted safe cellular therapy. Donor leukocyte infusions in the allogeneic hematopoietic transplant setting can provide a clinically relevant boost of immunity to reduce opportunistic infections and to increase graft-versus-leukemia activity. Our laboratory has a major focus toward ex vivo expansion of cord blood T cells with anti-apoptotic cytokines and CD3/CD28 co-stimulatory beads. Expanded lymphocytes lack alloreactivity against recipient and other allogeneic cells indicating a favorable safety profile from graft-versus-host disease. Nevertheless, expanded T cells can be primed subsequently against lymphoid and myeloid leukemia cells to generate tumor-specific cytotoxic T cells. These findings offer a major step in fulfilling critical biological requirements to quickly generate a cellular product ex vivo, using a negligible fraction of a cord blood graft that provides a flexible adoptive immunotherapy platform for both children and adults.