Advances in umbilical cord blood cell therapy: the present and the future

ABSTRACT

Introduction: Umbilical cord blood (UCB), previously seen as medical waste, is increasingly recognized as a valuable source of cells for therapeutic use. The best-known application is in hematopoietic stem cell transplantation (HSCT), where UCB has become an increasingly important graft source in the 28 years since the first umbilical cord blood transplantation (UCBT) was performed. Recently, UCB has been increasingly investigated as a putative source for adoptive cell therapy.

Areas covered: This review covers the advances in umbilical cord blood transplantation (UCBT) to overcome the limitation regarding cellular dose, immunological naivety and additional cell doses such as DLI. It also provides an overview regarding the progress in adoptive cellular therapy using UCB.

Expert opinion: UCB has been established as an important source of stem cells for HSCT. Successful strategies to overcome the limitations of UCBT, such as the limited cell numbers and naivety of the cells, are being developed, including novel methods to perform in vitro expansion of progenitor cells, and to improve their homing to the bone marrow. Promising early clinical trials of adoptive therapies with UCB cells, including non-immunological cells, are currently performed for viral infections, malignant diseases and in regenerative medicine.

KEYWORDS:

• Cord blood transplantation
• adoptive cell therapy
• HLA
• lymphocytes
• clinical trials

Article highlights

• Umbilical cord blood (UCB) is a valuable and easily accessed source of cells for cellular therapy.

• Umbilical cord blood transplantation (UCBT) has several advantages, such as permissibility for HLA mismatch and a low risk for GVHD, but also disadvantages, including low cell dose, slow engraftment and increased risk for non-relapse mortality.

• Approaches to improve UCBT outcome include double cord blood transplantation, which has been implemented into clinical practice with excellent results. In vitro expansion of hematopoietic progenitor cells, and improved homing capacity to the bone marrow, have also been studied with good results.

• Several promising UCB-based adoptive immune cell therapies are in early clinical or preclinical development, such as UCB T cells bearing chimeric antigen receptors, in vitro cultured antigen-specific T cells against virus- and tumor-associated antigens, and NK cell therapies.

• Therapies with non-immunological cells, such UCB-derived mesenchymal stromal cell and endothelial-like vascular progenitors, are in early clinical and in preclinical development in regenerative medicine.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors are funded by grants KP2016-0027 from the Barncancerfonden and 2014-1839 from Vetenskapsrådet.