Advances in adoptive immunotherapy to accelerate T-cellular immune reconstitution after HLA-incompatible hematopoietic stem cell transplantation.
Although partially HLA-mismatched hematopoietic stem cell transplantation (HSCT) has become an important therapeutic option for children with primary immunodeficiencies, delayed reconstitution of the T-cell compartment remains a major clinical concern. Adoptive immunotherapies to provide recipients with a protective and diverse T-cell repertoire in the months following HSCT are warranted. In order to improve T-cell reconstitution after T-cell-depleted HSCT, different strategies are currently being studied. Some are based on administration of modified mature T cells (e.g., allodepleted T cells or pathogen-specific T cells). Others aim at accelerating de novo thymopoiesis from donor-derived hematopoietic stem cells in vivo via the administration of thymopoietic agents or the transfer of large numbers of T-cell precursors generated ex vivo. The present article will provide a brief summary of recent advances in the field of allodepletion and adoptive transfer of pathogen-specific T cells and a detailed discussion of strategies for enhancing thymopoiesis in vivo.
Reimann
Christian
C
Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biothérapie, Hopital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, and Université Paris Descartes 75015 Paris, France.
Dal Cortivo
Liliane
L
Hacein-Bey-Abina
Salima
S
Fischer
Alain
A
André-Schmutz
Isabelle
I
Cavazzana-Calvo
Marina
M
D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000639:trends; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation