Umbilical cord blood derived cellular therapy: advances in clinical development

Abstract

While cord blood (CB) is primarily utilized in allogeneic hematopoietic cell transplantation (HCT), the development of novel cell therapy products from CB is a growing and developing field. Compared to adult blood, CB is characterized by a higher percentage of hematopoietic stem cells (HSCs) and progenitor cells, less mature immune cells that retain a high capacity of proliferation, and stronger immune tolerance that requires less stringent HLA-matching when used in the allogenic setting. Given that CB is an FDA regulated product and along with its unique cellular composition, CB lends itself as a readily available and safe starting material for the development of off-the-shelf cell therapies. Moreover, non-hematologic cells such as mesenchymal stem cell (MSCs) residing in CB or CB tissue also have potential in regenerative medicine and inflammatory and autoimmune conditions. In this review, we will focus on recent clinical development on CB-derived cellular therapies in the field of oncology, including T-cell therapies such as chimeric antigen receptor (CAR) T-cells, regulatory T-cells, and virus-specific T-cells; NK-cell therapies, such as NK cell engagers and CAR NK-cells; CB-HCT and various modifications; as well as applications of MSCs in HCT.

Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model

“…The scientific literature highlights the significant potential of umbilical cord blood (UCB) as a valuable source of stem cells with tolerogenic and immunomodulatory properties [38][39][40]. UCB serves as a source of mesenchymal stem cells [41][42][43] and progenitor hematopoietic cells [44][45][46]. Notably, UCB presents distinct advantages over bone marrow transplants, including lower immunogenicity levels [47][48][49] and reduced requirements for HLA matching [50][51][52], thereby broadening the pool of potential donors and improving accessibility to transplantation and tissue regeneration.…”

Perspectives for the Use of Umbilical Cord Blood in Transplantation and Beyond: Initiatives for an Advanced and Sustainable Public Banking Program in Greece

“…The high rejection rate of the donated UCB units due to the strict acceptance criteria for HSCT purposes, in association with the high application of the haploidentical HSCT, have resulted in a significant limitation of the UCB use in the clinic, with a consequent impact on the economic sustainability of the public UCB banks. The perspective of recycling the inappropriate for HSCT units or using the high-quality excess units for isolation and expansion of immune and stem cell populations for cell engineering/reprogramming processes and for production of cell-derivatives for research and clinical applications, extends the therapeutic value of the UCB and increases the sustainability potential of the UCB banks [18,[21][22][23]35,[38][39][40][41][42]52,65,68,70,75,[78][79][80][81][82][83][84][85][86][97][98][99][100]. Novel applications in adoptive immunotherapy, regenerative medicine and specialized transfusion are anticipated not only to maximize the use of the UCB but also to minimize the financial deficit of the public UCB banks through reimbursement procedures.…”

Challenges and new technologies in adoptive cell therapy

“…However, PB is not the optimal cell source because it contains few NK cells. In contrast to PB, UCB contains a large amount of NK cells with greater proliferation potential than those from PB, making it a more feasible source for creating CAR-NK cells [ 321 ]. Clinical trials for CAR-NK cells generated from UCB are currently being conducted and showed good safety and efficacy [ 319 , 322 ].…”