Cord Blood Inventory: Future Opportunities

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Jessica Sue, BSc, MHSM
Junior Associate Editor (ESP Leadership Development Program ), ISCT Telegraft
Sydney Cord Blood Bank, Sydney Children’s Hospitals Network
Australia

The World Marrow Donor Association (WMDA), a global organization that operates the world’s largest hematopoietic stem cell database, currently lists 755, 016 cord blood units (CBU) as part of the inventory, allowing clinical programs worldwide to identify CBU for patients requiring a hematopoietic stem cell transplant via their Search & Match service^1,². These CBU, which are manufactured from cord blood (CB) collected by public cord blood banks (CBB), are donated voluntarily and tissue typed, with many tested and cryopreserved under stringent standards, such as those required by international accreditation body the Foundation for the Accreditation of Cellular Therapy (NetCord-FACT)³.

CBUs listed on this inventory are primarily used for allogeneic hematopoietic stem cell transplant (HSCT) to treat acute and chronic leukemias, lymphomas, bone marrow failure syndromes, inherited metabolic disorders and primary immunodeficiencies. Since the first HSCT using cord blood (cord blood transplant; CBT) in 1988, there have been more than 50,000 CBTs performed worldwide. However, factors such as delayed engraftment compared to adult donor sources, alternative treatment options such as haploidentical transplants, and improvements in chemotherapeutic and post-transplant protocols, there has been an overall reduction in CBU being selected as a treatment option over the last decade⁴, and some cord blood banks have withdrawn from the WMDA registry. As such, many of the 755,016 CBU on the WMDA database will potentially sit unused, leading to the question – can this inventory be strategically repurposed under clinical governance and ethical frameworks? In my view, the answer is yes: CBU are a valuable and unique resource of good manufacturing practice (GMP) grade cells that can be considered for a range of applications. CBU expressing more commonly represented tissue types with relatively low cell counts can be strategically diverted to alternative uses, allowing higher utility CBU (less common tissue types and higher cell counts) to be kept available for current and emerging therapies⁵.

Utilization of CBB Inventory

Improvements in Cord Blood Banking

Within the CBB itself, cryopreserved CBU can be used for training staff in handling cryopreserved products, thawing of CBU and associated samples, QC testing and compliant packing and transport to clinical programs. For clinical programs, NetCord-FACT accredited CBBs can provide ‘practice CBU’, allowing them to perform competency training in CBU thawing and washing for staff. This is particularly useful if the clinical programs do not perform CBU thawing process on a regular basis, giving assurance to the program that staff know how to handle the CBU product appropriately prior to being administered to a patient.

An important quality control activity at CBBs, required by regulatory bodies, is the conduct of thaw assessments of cryopreserved CBU and representative samples, especially as part of a stability program supporting long term storage and establishing expiry dates. The analysis and trending of results can be used to ensure CBU being stored long term in liquid nitrogen tanks remain clinically viable, and that the processing and cryopreservation methods used – particularly if they have evolved over time – properly preserve cell function. This can allow CBBs to monitor and detect any changes in product quality over time that may be associated with processing methods, equipment or storage conditions.

New Age Therapies

Appropriately consented, cryopreserved CBU can be made available to researchers performing ethically approved research studies, especially for those who are seeking a source of GMP-grade, characterized material.

Cryopreserved CBU can be used to optimize new thawing protocols or evaluation of potency assays, and the cells found in CBU are commonly used for in vitro and in vivo disease modelling.

Tissue typed and cryopreserved CBU are an effective starting material for iPSCs, due to their naivety and ability to be easily programmed (compared to adult derived stem cells). Once developed, iPSCs have a spectrum of uses, from genetic and hematological disease modeling to development of banks of tissue typed GMP compliant iPSCs available for development of allogeneic off-the-shelf therapies.

Post-thaw of cryopreserved CBU, immune cells can be isolated, including T-cells and natural killer (NK) cells, allowing them to be used in development of off-the-shelf therapies for treatment of conditions such as graft-versus-host disease (regulatory T cells) or various cancer immunotherapies (T and NK cells, including chimeric antigen receptor-modified). Benefits to utilizing cord blood inventory for these therapies include; (1) potentially higher proliferative potential compared to adult cells due to naivety, and (2) availability of HLA typing to enable selection of suitable donors (e.g., HLA matching, HLA expression of antigen peptides for cytotoxic T lymphocytes).

Beyond traditional HSCT, CB continues to be investigated for its therapeutic potential in regenerative and immunomodulatory medicine, with a range of early phase clinical trials being conducted worldwide for conditions such as perinatal brain injury, neonatal stroke and cerebral palsy. As both autologous and allogeneic donor sources are being studied, CBU on existing donor inventories can be provided to support clinical trials, allowing access to a cell source that is highly characterized, safe, and quality-assured.

Final Thoughts

For CBBs interested in strategically and ethically repurposing their inventory, there are some actions that can be taken:

Considered classification of the inventory into categories of potential use, such as; transplant, product development, research, and quality control.
Analysis of consents used over different time periods to ensure support of alternative use of CBUs, particularly if the units were collected with the intention to be used for allogeneic hematopoietic stem cell transplant. This consideration can be extended to ensuring that current or future consents are appropriately broad and informative for likely current and prospective use cases.
Establish collaborations with academic institutions or other industry partnerships that can assist with progression of product development.

The reduction in rate of CBT does not foreshadow an obsolescence of the current worldwide CBU inventory, nor of CBBs themselves, particularly if steps are taken to strategically reposition inventory and diversify the applications for this public asset. Cryopreserved CBU, both retrospectively and prospectively banked, can be used to support training and education within CBBs and laboratories associated with clinical programs, and quality control initiatives to demonstrate ongoing suitability of cells for transplantation or infusion. CB cells are desirable starting material various therapies, and clinical trials continue to establish their use in conditions outside of standard of care therapies.