Advances in Adoptive Immunotherapy to Accelerate T-Cellular Immune Reconstitution After Hla-Incompatible Hematopoietic Stem Cell Transplantation

Abstract

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.

KEYWORDS::

• allodepletion
• cytotoxic lymphocyte
• ex vivo T-cell precursor generation
• immune reconstitution after HSCT
• post-transplant immunodeficiency
• primary immunodeficiency

Financial & competing interests disclosure

Christian Reimann was funded by a scholarship from the German Research Foundation (DFG). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. We thank David Fraser for his language editing review.

Additional information

Funding

Christian Reimann was funded by a scholarship from the German Research Foundation (DFG). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript. We thank David Fraser for his language editing review.