Cytotherapy Corner
Donald G. Phinney, PhD
Senior Editor
The Scripps Research Institute-Scripps Florida
Jupiter, FL, USA
In this edition of Cytotherapy Corner, I am pleased to introduce our new Assistant Editor, Dr. Rachel A. Burga. Rachel received her BSc degree in Biomedical Engineering from Columbia University, a PhD in Microbiology, Immunology and Tropical Medicine from George Washington University and is currently employed as a Senior Scientist in Cell Therapy at Obsidian Therapeutics. Rachel came on board last month and as evidenced by her credentials, brings a lot of relevant experience to the journal. As Assistant Editor, she will work closely with myself and our Commissioning Editor, Dr. Patrick Hanley, to raise awareness of the Cytotherapy brand. She will also help in recruiting outstanding content for the journal and work closely with the ISCT membership to ensure that the journal continues to support the mission of the society. I hope everyone will join me in welcoming Rachel to our impressive team of Cytotherapy Editors.
In the February 2022 issue, I want to highlight an article by Abdel-Azim et al., titled “Alignment of Practices for Data Harmonization Across Multi-Center Cell Therapy Trials: A Report from the Consortium for Pediatric Cellular Immunotherapy.” This paper, which is authored by participating members of the Consortium for Pediatric Cellular Immunotherapy (CPCI), outlines strategies that enable better harmonization of data from multi-center trials involving immune effector cells (IEC) therapies. Herein, the authors analyzed SOPs from several CPCI sites with the intent of identifying commonalities and differences in sample handling to identify best practice recommendations to promote consistency across multi-center trials. Specific emphasis was placed on evaluating key pre-analytic variables, such as specimen collection, shipping, processing, and cytokine and flow-based sample analysis. The authors identified specific gaps in specimen collection, such as time points, type of anticoagulant employed, and methods used to assess cytokines. Other critical variables included incubation time between sample collection and processing to ensure the stability of key biomarkers, use of fresh vs. frozen samples, selection of relevant cytokines for cytokine profiling of participant-derived plasma and methods of analyzing these cytokine biomarkers in biological samples.
While this study is of keen interest to those involved in IEC therapies, I found the paper to have much broader appeal. For example, while efforts to harmonize practices across sites participating in multi-center trials are critically needed to produce top line data, this need extends far beyond IEC therapies. Indeed, the lack of data harmonization has significantly hampered efforts to evaluate the potency and efficacy of mesenchymal stem/stromal cell (MSC)-based therapies. Specifically, the lack of standardization in practices for donor selection, culture expansion including media formulation, plating density, etc., metrics to assess product composition of matter and biological potency, dosing, and use of fresh or cryopreserved products are just some of the variables that hamper efforts to evaluate product potency and efficacy across multiple trials and patients. Therefore, the adoption of standardized best practices for MSC-based products is necessary to establish specific patient populations that may benefit from these products and establish regimens that yield reliable and reproducible clinical outcomes.
I would also like to highlight a paper by Leonard et al., titled “Curative Therapy for Hemoglobinopathies: an ISCT Stem Cell Engineering Committee Review Comparing Outcomes, Accessibility, and Cost of ex vivo Stem Cell Gene Therapy vs. Allogeneic Hematopoietic Stem Cell Transplantation”. This paper briefly summarizes the benefits and limitations of existing disease-modifying therapies for patients with thalassemia major and sickle cell disease (SCD), and for hematopoietic stem cell transplantation (HSCT), which represents a curative therapy. The authors then describe in detail the nuances of HSCT for this patient population including disease complications that limit therapy effectiveness, preparative regimens used for these patient populations, differences in the effectiveness of HLA-matched sibling donor vs. matched unrelated donor transplants along with the risks and limitations associated with the use of matched unrelated donors. The authors then give an overview of emerging alternative treatments including gene transfer and gene editing approaches for both patient populations and then provide an evidence-based assessment of the effectiveness of HSCT vs. gene therapies in patients, which includes evaluations of overall risk-benefit, patient eligibility, patient follow-up needs and therapy costs. Overall, the paper is expertly written, highly informative, and nicely illustrates how advancements in transplant medicine have led to curative therapies for some thalassemia and SCD patients, and how advancements in gene therapies may provide a universal cure for patients with hereditary hemoglobinopathies.
Happy reading.
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