Anticancer cellular immunotherapies derived from umbilical cord blood

ABSTRACT

Introduction: The lack of highly effective drugs in many malignancies has prompted scientific interest in the development of alternative treatment strategies. Cellular immunotherapy involving the adoptive transfer of immune cells that potently recognize and eliminate malignantly transformed cells has become a promising new tool in the anticancer armory. Studies suggest that the unique biological properties of umbilical cord blood (UCB) cells could precipitate enhanced anticancer activity; hence, UCB could be an optimal source for immunotherapy with the potential to provide products with ‘off-the-shelf’ availability.

Areas covered: In this review, the authors summarize data on the transfer of naturally occurring or genetically modified UCB cells to treat cancer. The focus within is on the phenotypic and functional differences compared to other sources, the alloreactive and anticancer properties, and manufacturing of these products. Therapies utilizing cytokine-induced killer (CIK) cells, natural killer (NK) cells and chimeric antigen receptor (CAR) T-cells, are discussed.

Expert opinion: The cellular immunotherapy field has become a growing, exciting area that has generated much enthusiasm. There is evidence that anticancer immunotherapy with UCB-derived products is feasible and safe; however, considering the limited number of clinical trials using UCB-derived products, further studies are warranted to facilitate translation into clinical practice.

KEYWORDS:

• Anticancer immunotherapy
• umbilical cord blood
• cytokine-induced killer (CIK) cells
• natural killer (NK) cells
• chimeric antigen receptor (CAR) T cells

Article highlights

• The rationale behind anticancer cellular immunotherapy is the ability of immune cells to recognize and eliminate malignantly transformed cells.

• Umbilical cord blood (UCB) is widely used as an alternative stem cell source for allogeneic hematopoietic stem cell transplantation. Its abundance of progenitor cells with anticancer potential makes UCB attractive for immunotherapy development.

• Techniques have been established to overcome the limited number and immaturity of UCB cells. Data suggest that activated UCB-derived cells might mediate superior tumor-killing activity compared with other sources.

• Cytokine-induced killer (CIK) cells are a heterogeneous population of cells originating from T-lymphocytes that exhibit anticancer activity in a non-major histocompatibility complex (MHC)-restricted manner. Experience with UCB-derived CIK cells in a limited number of cancer patients confirms some clinical effectiveness.

• Natural killer (NK) cells are CD56+/CD3- lymphocytes of the innate immune system that play a fundamental role in cancer surveillance. Studies utilizing UCB-derived NK cells confirm the feasibility and safety of the modality, and further studies are under way to investigate its efficacy.

• Patients with acute lymphoblastic leukemia have achieved excellent complete remission rates with genetically engineered T-cell therapy. The modality has been intensively tested for other diseases. UCB-derived T-cells can be successfully modified to express chimeric antigen receptors, and results from clinical trials are awaited.

• Universal, Good Manufacturing Practice-compliant, ‘off-the-shelf’ immunotherapy products might become available in the near future, enabling wider access to cellular immunotherapy.

This box summarizes key points contained in the article.

Declaration of interest

K Balassa receives a fellowship from NHS Blood and Transplant while V Rocha is a principal investigator for NHS Blood and Transplant. 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.

Additional information

Funding

This work was supported by NHS Blood and Transplant (NHSBT).