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Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy
A major complication of chimeric antigen receptor (CAR) T-cell therapy is immune effector cell–associated neurotoxicity syndrome (ICANS), which presents as aphasia, confusion, weakness, somnolence, seizures, and coma. This is similar to the neurologic manifestations of hypophosphatemia, which can re...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for Cancer Research
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722515/ https://www.ncbi.nlm.nih.gov/pubmed/36259217 http://dx.doi.org/10.1158/2326-6066.CIR-22-0418 |
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author | Tang, Jack Pengfei Peters, Cole W. Quiros, Crystal Wang, Xiaoyan Klomhaus, Alexandra M. Yamada, Reiko E. Timmerman, John M. Moore, Theodore B. Nowicki, Theodore S. |
author_facet | Tang, Jack Pengfei Peters, Cole W. Quiros, Crystal Wang, Xiaoyan Klomhaus, Alexandra M. Yamada, Reiko E. Timmerman, John M. Moore, Theodore B. Nowicki, Theodore S. |
author_sort | Tang, Jack Pengfei |
collection | PubMed |
description | A major complication of chimeric antigen receptor (CAR) T-cell therapy is immune effector cell–associated neurotoxicity syndrome (ICANS), which presents as aphasia, confusion, weakness, somnolence, seizures, and coma. This is similar to the neurologic manifestations of hypophosphatemia, which can result from sudden increases in metabolic demand for phosphorylated intermediates (e.g., refeeding syndrome and sepsis). Given these similarities, we investigated whether CAR T-cell effector metabolic activity is associated with increased extracellular phosphate consumption and a possible association between hypophosphatemia and ICANS. In vitro 4–1BB and CD28 CD19-targeted CAR T-cell effector activity was found to be associated with increased consumption of media phosphorus, which was temporally associated with increased single-cell effector secretomic activity and increased phosphorus-dependent metabolic demand of the CAR T cells. A clinical cohort of 77 patients treated with CD19-targeted CAR T-cell therapy demonstrated a significant anticorrelation between serum phosphorus and ICANS incidence and severity, with earlier onset of hypophosphatemia after CAR T-cell infusion more likely to result in neurotoxicity. These results imply phosphorous level monitoring could alert to the development of ICANS in clinical scenarios. See related Spotlight by Tobin et al., p. 1422 |
format | Online Article Text |
id | pubmed-9722515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-97225152022-12-12 Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy Tang, Jack Pengfei Peters, Cole W. Quiros, Crystal Wang, Xiaoyan Klomhaus, Alexandra M. Yamada, Reiko E. Timmerman, John M. Moore, Theodore B. Nowicki, Theodore S. Cancer Immunol Res Priority Brief A major complication of chimeric antigen receptor (CAR) T-cell therapy is immune effector cell–associated neurotoxicity syndrome (ICANS), which presents as aphasia, confusion, weakness, somnolence, seizures, and coma. This is similar to the neurologic manifestations of hypophosphatemia, which can result from sudden increases in metabolic demand for phosphorylated intermediates (e.g., refeeding syndrome and sepsis). Given these similarities, we investigated whether CAR T-cell effector metabolic activity is associated with increased extracellular phosphate consumption and a possible association between hypophosphatemia and ICANS. In vitro 4–1BB and CD28 CD19-targeted CAR T-cell effector activity was found to be associated with increased consumption of media phosphorus, which was temporally associated with increased single-cell effector secretomic activity and increased phosphorus-dependent metabolic demand of the CAR T cells. A clinical cohort of 77 patients treated with CD19-targeted CAR T-cell therapy demonstrated a significant anticorrelation between serum phosphorus and ICANS incidence and severity, with earlier onset of hypophosphatemia after CAR T-cell infusion more likely to result in neurotoxicity. These results imply phosphorous level monitoring could alert to the development of ICANS in clinical scenarios. See related Spotlight by Tobin et al., p. 1422 American Association for Cancer Research 2022-12-02 2022-10-19 /pmc/articles/PMC9722515/ /pubmed/36259217 http://dx.doi.org/10.1158/2326-6066.CIR-22-0418 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
spellingShingle | Priority Brief Tang, Jack Pengfei Peters, Cole W. Quiros, Crystal Wang, Xiaoyan Klomhaus, Alexandra M. Yamada, Reiko E. Timmerman, John M. Moore, Theodore B. Nowicki, Theodore S. Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy |
title | Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy |
title_full | Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy |
title_fullStr | Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy |
title_full_unstemmed | Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy |
title_short | Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy |
title_sort | hypophosphatemia due to increased effector cell metabolic activity is associated with neurotoxicity symptoms in cd19-targeted car t-cell therapy |
topic | Priority Brief |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722515/ https://www.ncbi.nlm.nih.gov/pubmed/36259217 http://dx.doi.org/10.1158/2326-6066.CIR-22-0418 |
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