Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells
BackgroundChimeric antigen receptor-T (CAR-T) cells have transformed the treatment of human B cell malignancies. With the advent of CAR-T therapy, specific and in some cases severe toxicities have been documented with cytokine release syndrome (CRS) being the most frequently reported. As dogs develo...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2022.824982/full |
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| author | Matthew J. Atherton Matthew J. Atherton Antonia Rotolo Kumudhini P. Haran Nicola J. Mason Nicola J. Mason Nicola J. Mason |
| author_facet | Matthew J. Atherton Matthew J. Atherton Antonia Rotolo Kumudhini P. Haran Nicola J. Mason Nicola J. Mason Nicola J. Mason |
| author_sort | Matthew J. Atherton |
| collection | DOAJ |
| description | BackgroundChimeric antigen receptor-T (CAR-T) cells have transformed the treatment of human B cell malignancies. With the advent of CAR-T therapy, specific and in some cases severe toxicities have been documented with cytokine release syndrome (CRS) being the most frequently reported. As dogs develop tumors spontaneously and in an immunocompetent setting, they provide a unique translational opportunity to further investigate the activity and toxicities associated with CAR-T therapy. Although various adoptive cellular therapy (ACT) trials have been documented and several more are ongoing in canine oncology, CRS has not been comprehensively described in canine cancer patients.Case PresentationHere we present the clinical and serologic changes in a dog treated with autologous CAR-T for relapsed B cell lymphoma that presented with lethargy and fever 3 days following CAR-T. Multiplexed serum cytokine profiling revealed increases in key cytokines implicated in human CRS including IL-6, MCP-1, IFNγ and IL-10 at or shortly after peak CAR-T levels in vivo.ConclusionThe observations noted in this case report are consistent with CRS development following CAR-T therapy in a canine patient. The dog represents a compelling model to study the pathophysiology of CRS and pre-clinically screen novel therapeutics to prevent and treat this life-threatening condition in the setting of a complex and naturally evolved immune system. |
| first_indexed | 2024-12-11T14:59:16Z |
| format | Article |
| id | doaj.art-0117d45348934ecc9f26ef93915102d6 |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-12-11T14:59:16Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-0117d45348934ecc9f26ef93915102d62022-12-22T01:01:12ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692022-07-01910.3389/fvets.2022.824982824982Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T CellsMatthew J. Atherton0Matthew J. Atherton1Antonia Rotolo2Kumudhini P. Haran3Nicola J. Mason4Nicola J. Mason5Nicola J. Mason6Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesParker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesBackgroundChimeric antigen receptor-T (CAR-T) cells have transformed the treatment of human B cell malignancies. With the advent of CAR-T therapy, specific and in some cases severe toxicities have been documented with cytokine release syndrome (CRS) being the most frequently reported. As dogs develop tumors spontaneously and in an immunocompetent setting, they provide a unique translational opportunity to further investigate the activity and toxicities associated with CAR-T therapy. Although various adoptive cellular therapy (ACT) trials have been documented and several more are ongoing in canine oncology, CRS has not been comprehensively described in canine cancer patients.Case PresentationHere we present the clinical and serologic changes in a dog treated with autologous CAR-T for relapsed B cell lymphoma that presented with lethargy and fever 3 days following CAR-T. Multiplexed serum cytokine profiling revealed increases in key cytokines implicated in human CRS including IL-6, MCP-1, IFNγ and IL-10 at or shortly after peak CAR-T levels in vivo.ConclusionThe observations noted in this case report are consistent with CRS development following CAR-T therapy in a canine patient. The dog represents a compelling model to study the pathophysiology of CRS and pre-clinically screen novel therapeutics to prevent and treat this life-threatening condition in the setting of a complex and naturally evolved immune system.https://www.frontiersin.org/articles/10.3389/fvets.2022.824982/fullCAR-T cellscytokine release syndrome (CRS)canine B cell lymphomacomparative oncologyspontaneous tumor model |
| spellingShingle | Matthew J. Atherton Matthew J. Atherton Antonia Rotolo Kumudhini P. Haran Nicola J. Mason Nicola J. Mason Nicola J. Mason Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells Frontiers in Veterinary Science CAR-T cells cytokine release syndrome (CRS) canine B cell lymphoma comparative oncology spontaneous tumor model |
| title | Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells |
| title_full | Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells |
| title_fullStr | Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells |
| title_full_unstemmed | Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells |
| title_short | Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells |
| title_sort | case report clinical and serological hallmarks of cytokine release syndrome in a canine b cell lymphoma patient treated with autologous car t cells |
| topic | CAR-T cells cytokine release syndrome (CRS) canine B cell lymphoma comparative oncology spontaneous tumor model |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2022.824982/full |
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