Enhancing T cell reconstitution after hematopoietic stem cell transplantation: a brief update of the latest trends.
Hematopoietic stem cell transplantation (HSCT) is associated with a period of immune incompetence that particularly affects the T cell lineage. Strategies to enhance T cell reconstitution could significantly improve the survival of HSCT recipients by decreasing the incidence of fatal infectious complications and by enhancing graft-versus-tumor activity. In recent years, a variety of promising strategies have been established in preclinical models to improve T cell recovery in particular after allogeneic T cell-depleted HSCT, without aggravating graft-versus-host disease while preserving or even improving graft-versus-tumor activity. These therapies include treatment with keratinocyte growth factor (KGF), growth hormone (GH), LHRH agonists, interleukin 7 (IL-7) and interleukin 15 (IL-15). Thanks to the establishment of Notch-based culture systems, adoptive cellular therapies with T lineage-committed precursor cells have become feasible, since early T cell progenitors can now easily be generated in vitro in large quantities and have been proven to be very effective in enhancing T cell reconstitution and anti-tumor activity after allogeneic T cell-depleted HSCT. The translation of most of these strategies into clinical trials is likely and in some cases Phase I/II studies are already underway.
Zakrzewski
Johannes L
JL
Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, Zuckerman Research Center, New York, NY 10021, USA.
Goldberg
Gabrielle L
GL
Smith
Odette M
OM
van den Brink
Marcel R M
MR
D018929:Cell Culture Techniques; D018380:Hematopoietic Stem Cell Transplantation / Q000639:trends*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007107:Immune System / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*
D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins