Allogeneic cell therapy development has been top-of-mind in recent years as autologous cell therapies see continued success. But there is an allogeneic cell therapy that has already been used for decades: hematopoietic stem cell transplantation (HSCT).
Over those decades a team has quietly worked behind the scenes to create the tools and expertise needed to find the best donor to meet a patient’s needs. And that expertise holds value for allogeneic cell and gene therapy developers, too.
The team is the Clinical HLA Services team at the National Marrow Donor Program® (NMDP)/Be The Match®. (Be The Match BioTherapies® is part of the NMDP/Be The Match.)
The people behind the science of cell source selection
The Clinical HLA Services team is the largest group of human leukocyte antigen (HLA) experts in the world. It includes the Search Strategy and Registry Data Quality teams.
“Most HLA experts are working in isolation or on a team of less than a handful. Our team is highly trained and about half of the team holds advanced degrees, including PhDs, master’s degrees and medical degrees. This depth and breadth of experience allow us to provide a full scope of services to any cell therapy company needing advice or capabilities around histocompatibility,” shared Craig Malmberg, Senior Manager of Clinical HLA Services.
All day, every day a team of 21 people look at questions of histocompatibility and immunogenetics to find the best cell source for a patient or cell and gene therapy developer. Those cell sources commonly include peripheral blood stem cells from adult volunteer donors or umbilical cord blood units.
The evolution of cell source selection in allogeneic cell therapy development
New technologies may allow cell and gene therapy companies to work around some immunologic response. However, HLA’s future impact on allogeneic cell therapy development isn’t fully known. For example, HLA expression that is retained as part of the effector mechanism could lead to rejection. That’s why the expertise of the Clinical HLA Services team is so important.
“Thinking about how cell therapies are evolving, we need to ensure that cell therapy products are not rejected for histocompatibility reasons. We believe an important part of cell therapy could be to look at what we call a ‘donor-specific antibody assessment’ in the unrelated HSCT field,” Malmberg explained.
“Patients still have anti-HLA antibodies that can react to histocompatibility antigens that are carried on the infused cell therapy product. That may provide a mechanism of rejection of the cell therapy product,” he added.
Malmberg’s team has been key in developing an automated virtual cross-match capability for allogeneic HSCT that offers direction in selecting cell sources that would not be rejected. It’s an area he believes warrants investigation in the allogeneic cell and gene therapy space, too.
“There hasn’t been a systematic study looking at how anti-HLA antibodies in patients impact cell therapy durability. It’s a question that is important to answer,” he said.
HLA and histocompatibility expertise bridges a gap for cell therapy developers
The expertise of the Clinical HLA Services team complements the expertise of immunology teams at a cell and gene therapy company.
“HLA is the most complex, highly variable part of the entire immune system. It has a complex nomenclature that creates a barrier to entry. That makes it very difficult for immunologists and geneticists to gain that deep experience with histocompatibility. Our team bridges that gap,” Malmberg explained.
For example, the team provides histocompatibility support—such as HLA and KIR matching—for Be The Match BioTherapies clients to ensure their donor source selection requirements are being met.
Be The Match BioTherapies offers allogeneic cell therapy developers access to the millions of donors on the Be The Match Registry®. That makes the expertise of the Clinical HLA Services team especially valuable.
“There’s no other cell bank and no other resource like our donors. We have the world’s largest team of experts that know how to sort through millions of donors to find the one that best meets a client’s needs,” Malmberg said.
High-quality registry data allows for informed decision making
Registry data quality is another critical service the Clinical HLA Services team offers. Most laboratories and transplant centers submit HLA data and genetic information electronically through a custom developed secure gateway utilizing an xml–based data standard, histoimmunogenetic markup language (hml).
All received data undergoes automated quality control and comparison to existing data, if available, and is ultimately curated by Registry Data Quality team for use across all systems. That ensures that the data displayed is of the highest quality and reliability. This allows allogeneic cell therapy clients to make informed decisions when viewing potential cell sources
“The scope of the data we manage has grown over time. You can almost think of the HLA data as metadata that is being used to assess other matching attributes and qualifications. For example, B-leader and DP expression are newer concepts of matching in the HLA field. Our team has the capability of using and assessing that data in novel ways,” Malmberg explained.
His team also works closely with the Bioinformatics team that built an imputation method for matching to normalize the registry data and provide consistency. Imputation is necessary because data on the registry were collected over decades. Technologies have changed and more information is now available than with past testing methodologies.
As the matching algorithm, called HapLogicSM, evolves to provide the prediction of missing data, the Data Quality team ensures the data used for those predictions and the output of those predictions are consistent over time and validated against real-life examples.
The role histocompatibility may play in future allogeneic cell therapy development
As Malmberg looks at how the allogeneic cell therapy field is evolving and the challenges ahead, he believes the Clinical HLA Services team is well-positioned to support allogeneic cell and gene therapy developers.
“I had the opportunity to attend ISCT 2022. A lot of the discussion around the fate of allogeneic products was related to durability. That’s a question of immunologic compatibility, which is largely an extent of histocompatibility,” he said.
He added, “I’m looking forward to leveraging our team to help cell and gene therapy developers understand what makes the best cell graft for their product. This is the most talented group of professionals in the field of histocompatibility that you could possibly imagine. We are fully committed to serving patients because we know the direct impact this work has on a patient’s life.”
Your company can benefit from our team’s deep knowledge of HLA
Our team can support your needs whether you need:
- Consulting services to identify genetically compatible cell sources for your therapy
- Support for allogeneic cell sourcing from donor identification through coordination of cell collection and delivery
- A central point of access to fully characterized cord blood units
Request a call with our team. We’re ready to connect to discuss how we can help.