Highlights
- •Each T cell-based product requires product-specific quality control assays.
- •In vitro potency assays should reflect the anticipated in vivo mechanism of action.
- •Functionality assays based on the T cell cytotoxic potential are most evident.
- •Assay development needs T cell phenotype and anti-tumor cytotoxicity characterization.
- •Corroborated product-specific surrogate readouts may be appropriate.
Abstract
The adaptive immune system is known to play an important role in anti-neoplastic responses
via induction of several effector pathways, resulting in tumor cell death. Because
of their ability to specifically recognize and kill tumor cells, the potential use
of autologous tumor-derived and genetically engineered T cells as adoptive immunotherapy
for cancer is currently being explored. Because of the variety of potential T cell-based
medicinal products at the level of starting material and manufacturing process, product-specific
functionality assays are needed to ensure quality for individual products. In this
review, we provide an overview of in vitro potency assays suggested for characterization and release of different T cell-based
anti-tumor products. We discuss functional assays, as presented in scientific advices
and literature, highlighting specific advantages and limitations of the various assays.
Because the anticipated in vivo mechanism of action for anti-tumor T cells involves tumor recognition and cell death,
in vitro potency assays based on the cytotoxic potential of antigen-specific T cells are most
evident. However, assays based on other T cell properties may be appropriate as surrogates
for cytotoxicity. For all proposed assays, biological relevance of the tests and correlation
of the read-outs with in vivo functionality need to be substantiated with sufficient product-specific (non-)clinical
data. Moreover, further unraveling the complex interaction of immune cells with and
within the tumor environment is expected to lead to further improvement of the T cell-based
products. Consequently, increased knowledge will allow further optimized guidance
for potency assay development.
Key Words
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Article info
Publication history
Published online: March 26, 2018
Accepted:
January 27,
2018
Received:
December 11,
2017
Identification
Copyright
© 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
