T-cell Immunotherapies and the Role of Nonclinical Assessment: The Balance between Efficacy and Pathology

Toxicologic Pathology
Michaela E Sharpe

Abstract

Gene-engineered T-cell therapies have the potential to revolutionize the treatment of cancer. These therapies have shown exceptional clinical efficacy specifically in the field of B-cell malignancies and the first products (Kymriah™ and Yescarta™) have recently been approved in the United States for specific indications. The power of these treatments is also linked with a distinct set of toxicities both predicted and unpredicted, including off-tumor activity, cytokine release syndromes, and neurotoxicity, occasionally with fatal consequences. As these therapies begin to reach more patients, it is critical to develop the nonclinical tools to adequately determine the mechanisms driving these toxicities, to assess the safety risks of candidate products, and to develop strategies for safety management.

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Citations

Feb 15, 2019·Current Opinion in Pediatrics·DaMarcus E Baymon, Edward W Boyer
Oct 3, 2019·Cancers·Theodoulakis ChristofiApostolos Zaravinos
Apr 29, 2019·Cell Biology and Toxicology·Diane Catherine Wang, Xiangdong Wang
Oct 6, 2020·Frontiers in Immunology·María Tristán-ManzanoFrancisco Martin

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Methods Mentioned

BETA
transgenic
biopsies
genetic modification

Clinical Trials Mentioned

NCT00466531
NCT02631044
NCT01044069
NCT02535364
NCT01865617
NCT02348216
NCT02614066
NCT02030834
NCT02030847
NCT01029366

Software Mentioned

ScanProsite

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