TY - JOUR
T1 - Regulatory perspective on in vitro potency assays for human mesenchymal stromal cells used in immunotherapy
AU - de Wolf, Charlotte
AU - van de Bovenkamp, Marja
AU - Hoefnagel, Marcel C
N1 - Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
PY - 2017/7
Y1 - 2017/7
N2 - Mesenchymal stromal cells (MSCs) are multipotent cells derived from various tissues that can differentiate into several cell types. MSCs are able to modulate the response of immune cells of the innate and adaptive immune system. Because of these multimodal properties, the potential use of MSCs for immunotherapies is currently explored in various clinical indications. Due to the diversity of potential MSC medicinal products at the level of cell source, manufacturing process and indication, distinct functionality tests may be needed to ensure the quality for each of the different products. In this review, we focus on in vitro potency assays proposed for characterization and release of different MSC medicinal products. We discuss the most used functional assays, as presented in scientific advices and literature, highlighting specific advantages and limitations of the various assays. Currently, the most proposed and accepted potency assay for release is based on in vitro inhibition of T cell proliferation or other functionalities. However, for some products, assays based on other MSC or responder cell properties may be more appropriate. In all cases, the biological relevance of the proposed assay for the intended clinical activity should be substantiated with appropriate product-specific (non-)clinical data. In case practical considerations prevent the use of the ideal potency assay at release, use of a surrogate marker or test could be considered if correlation with functionality has been demonstrated. Nevertheless, as the field of MSC immunology is evolving, improvements can be expected in relevant assays and consequently in guidance related to potency testing.
AB - Mesenchymal stromal cells (MSCs) are multipotent cells derived from various tissues that can differentiate into several cell types. MSCs are able to modulate the response of immune cells of the innate and adaptive immune system. Because of these multimodal properties, the potential use of MSCs for immunotherapies is currently explored in various clinical indications. Due to the diversity of potential MSC medicinal products at the level of cell source, manufacturing process and indication, distinct functionality tests may be needed to ensure the quality for each of the different products. In this review, we focus on in vitro potency assays proposed for characterization and release of different MSC medicinal products. We discuss the most used functional assays, as presented in scientific advices and literature, highlighting specific advantages and limitations of the various assays. Currently, the most proposed and accepted potency assay for release is based on in vitro inhibition of T cell proliferation or other functionalities. However, for some products, assays based on other MSC or responder cell properties may be more appropriate. In all cases, the biological relevance of the proposed assay for the intended clinical activity should be substantiated with appropriate product-specific (non-)clinical data. In case practical considerations prevent the use of the ideal potency assay at release, use of a surrogate marker or test could be considered if correlation with functionality has been demonstrated. Nevertheless, as the field of MSC immunology is evolving, improvements can be expected in relevant assays and consequently in guidance related to potency testing.
KW - cell-based therapy
KW - government regulation
KW - immunomodulation
KW - in vitro potency assays
KW - mesenchymal stromal cells
KW - quality control
U2 - 10.1016/j.jcyt.2017.03.076
DO - 10.1016/j.jcyt.2017.03.076
M3 - Article
C2 - 28457740
SN - 1465-3249
VL - 19
SP - 784
EP - 797
JO - Cytotherapy
JF - Cytotherapy
IS - 7
ER -