Cell-based treatments are vital components in the field of immune therapies for patients. Cell therapies have been used for the treatment of diseases such as cancer, autoimmune syndromes, modulation of infection, and repair and regeneration of damaged tissues. Cell therapies encompass a wide range of different approaches, including hematopoietic stem cells, T cells, natural killer (NK) cells, dendritic cells and macrophages, and non-immune cells such as mesenchymal stromal cells (MSC) and endothelial cells. T cells in particular have generated the greatest interest and development for therapeutic use. Virus-specific Cytotoxic T Lymphocytes (CTL) and Tumour-Infiltrating Lymphocytes (TIL) have shown significant effects in cancer treatment, but other subsets (for example gamma-delta T cells) and in particular genetically modified T cells (CAR-T cells) are now becoming the primary approach in T cell therapy of disease. MSC and endothelial cells also have enormous potential in tissue repair and regeneration.
The principal requirement that links all of the cell therapies is that they are appropriately characterized. Globally, regulators for cell therapies require evidence that the target cells are suitable and safe for use. Conventionally, the characterization of cell therapies is generally based on surface phenotype, assessed through flow cytometry, which with multi-parameter analysis is a powerful tool for analysis. The flow cytometric approach is essential for the establishment of parameters such as viability, lineage, activation, differentiation, and defining release criteria for cell products. However, it is not necessarily the optimal approach for determining the functionality or potency of the therapy.
Potency is defined by the FDA as “the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result”. The key issue is what kind of assays represent an appropriate test. Determining the mechanism of action via in vivo testing is challenging for most facilities to undertake due to the requirement for maintenance and care of multiple animal species and models, and the relevance of a xenobiotic system for determining therapeutic functionality in patients is still debated. Therefore the development of effective in vitro assays and surrogate markers of efficacy are essential for simplifying the use of new cellular therapies. This becomes even more relevant when we discuss the challenge of generating differentiated cell therapies from ES or iPSC-derived stem cell stocks. There may be strong similarities between stem-cell-derived products and conventionally-derived comparators at a phenotypic level. However, does this map on to functional capacity?
This issue seeks to highlight new approaches for in vitro testing of cell therapy material, and demonstrate the potential for surrogate markers as part of cell therapy Critical Quality Attributes. This research can then be used to offer evidence to regulators of function and potency in cell therapies, streamlining the route to clinical trials and standard use. We would like to welcome Original Research, Methods, Policy and Practice Reviews, and Perspectives manuscripts to this collection.
Topic Editor Dr. Alasdair R Fraser received financial support from DPFS in collaboration with Astra Zenec. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Cell-based treatments are vital components in the field of immune therapies for patients. Cell therapies have been used for the treatment of diseases such as cancer, autoimmune syndromes, modulation of infection, and repair and regeneration of damaged tissues. Cell therapies encompass a wide range of different approaches, including hematopoietic stem cells, T cells, natural killer (NK) cells, dendritic cells and macrophages, and non-immune cells such as mesenchymal stromal cells (MSC) and endothelial cells. T cells in particular have generated the greatest interest and development for therapeutic use. Virus-specific Cytotoxic T Lymphocytes (CTL) and Tumour-Infiltrating Lymphocytes (TIL) have shown significant effects in cancer treatment, but other subsets (for example gamma-delta T cells) and in particular genetically modified T cells (CAR-T cells) are now becoming the primary approach in T cell therapy of disease. MSC and endothelial cells also have enormous potential in tissue repair and regeneration.
The principal requirement that links all of the cell therapies is that they are appropriately characterized. Globally, regulators for cell therapies require evidence that the target cells are suitable and safe for use. Conventionally, the characterization of cell therapies is generally based on surface phenotype, assessed through flow cytometry, which with multi-parameter analysis is a powerful tool for analysis. The flow cytometric approach is essential for the establishment of parameters such as viability, lineage, activation, differentiation, and defining release criteria for cell products. However, it is not necessarily the optimal approach for determining the functionality or potency of the therapy.
Potency is defined by the FDA as “the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result”. The key issue is what kind of assays represent an appropriate test. Determining the mechanism of action via in vivo testing is challenging for most facilities to undertake due to the requirement for maintenance and care of multiple animal species and models, and the relevance of a xenobiotic system for determining therapeutic functionality in patients is still debated. Therefore the development of effective in vitro assays and surrogate markers of efficacy are essential for simplifying the use of new cellular therapies. This becomes even more relevant when we discuss the challenge of generating differentiated cell therapies from ES or iPSC-derived stem cell stocks. There may be strong similarities between stem-cell-derived products and conventionally-derived comparators at a phenotypic level. However, does this map on to functional capacity?
This issue seeks to highlight new approaches for in vitro testing of cell therapy material, and demonstrate the potential for surrogate markers as part of cell therapy Critical Quality Attributes. This research can then be used to offer evidence to regulators of function and potency in cell therapies, streamlining the route to clinical trials and standard use. We would like to welcome Original Research, Methods, Policy and Practice Reviews, and Perspectives manuscripts to this collection.
Topic Editor Dr. Alasdair R Fraser received financial support from DPFS in collaboration with Astra Zenec. The other Topic Editors declare no competing interests with regard to the Research Topic subject.