CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap
Chimeric antigen receptor (CAR-T) therapy has marked a paradigm shift in the treatment of hematological malignancies and represent a promising growing field also in solid tumors. Neurotoxicity is a well‐recognized common complication of CAR-T therapy and is at the forefront of concerns for CAR-based...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-06-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1206983/full |
| _version_ | 1797802640836395008 |
|---|---|
| author | Lidia Gatto Ilaria Ricciotti Alicia Tosoni Vincenzo Di Nunno Stefania Bartolini Lucia Ranieri Enrico Franceschi |
| author_facet | Lidia Gatto Ilaria Ricciotti Alicia Tosoni Vincenzo Di Nunno Stefania Bartolini Lucia Ranieri Enrico Franceschi |
| author_sort | Lidia Gatto |
| collection | DOAJ |
| description | Chimeric antigen receptor (CAR-T) therapy has marked a paradigm shift in the treatment of hematological malignancies and represent a promising growing field also in solid tumors. Neurotoxicity is a well‐recognized common complication of CAR-T therapy and is at the forefront of concerns for CAR-based immunotherapy widespread adoption, as it necessitates a cautious approach. The non-specific targeting of the CAR-T cells against normal tissues (on-target off-tumor toxicities) can be life-threatening; likewise, immune-mediate neurological symptoms related to CAR-T cell induced inflammation in central nervous system (CNS) must be precociously identified and recognized and possibly distinguished from non-specific symptoms deriving from the tumor itself. The mechanisms leading to ICANS (Immune effector Cell-Associated Neurotoxicity Syndrome) remain largely unknown, even if blood-brain barrier (BBB) impairment, increased levels of cytokines, as well as endothelial activation are supposed to be involved in neurotoxicity development. Glucocorticoids, anti-IL-6, anti-IL-1 agents and supportive care are frequently used to manage patients with neurotoxicity, but clear therapeutic indications, supported by high-quality evidence do not yet exist. Since CAR-T cells are under investigation in CNS tumors, including glioblastoma (GBM), understanding of the full neurotoxicity profile in brain tumors and expanding strategies aimed at limiting adverse events become imperative. Education of physicians for assessing individualized risk and providing optimal management of neurotoxicity is crucial to make CAR-T therapies safer and adoptable in clinical practice also in brain tumors. |
| first_indexed | 2024-03-13T05:08:46Z |
| format | Article |
| id | doaj.art-44e4e21e5df740de96857a2e68bdee90 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T05:08:46Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-44e4e21e5df740de96857a2e68bdee902023-06-16T05:33:03ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-06-011310.3389/fonc.2023.12069831206983CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gapLidia Gatto0Ilaria Ricciotti1Alicia Tosoni2Vincenzo Di Nunno3Stefania Bartolini4Lucia Ranieri5Enrico Franceschi6Department of Oncology, Azienda Unità Sanitaria Locale (AUSL) Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyNervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, ItalyDepartment of Oncology, Azienda Unità Sanitaria Locale (AUSL) Bologna, Bologna, ItalyNervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, ItalyNervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, ItalyNervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, ItalyChimeric antigen receptor (CAR-T) therapy has marked a paradigm shift in the treatment of hematological malignancies and represent a promising growing field also in solid tumors. Neurotoxicity is a well‐recognized common complication of CAR-T therapy and is at the forefront of concerns for CAR-based immunotherapy widespread adoption, as it necessitates a cautious approach. The non-specific targeting of the CAR-T cells against normal tissues (on-target off-tumor toxicities) can be life-threatening; likewise, immune-mediate neurological symptoms related to CAR-T cell induced inflammation in central nervous system (CNS) must be precociously identified and recognized and possibly distinguished from non-specific symptoms deriving from the tumor itself. The mechanisms leading to ICANS (Immune effector Cell-Associated Neurotoxicity Syndrome) remain largely unknown, even if blood-brain barrier (BBB) impairment, increased levels of cytokines, as well as endothelial activation are supposed to be involved in neurotoxicity development. Glucocorticoids, anti-IL-6, anti-IL-1 agents and supportive care are frequently used to manage patients with neurotoxicity, but clear therapeutic indications, supported by high-quality evidence do not yet exist. Since CAR-T cells are under investigation in CNS tumors, including glioblastoma (GBM), understanding of the full neurotoxicity profile in brain tumors and expanding strategies aimed at limiting adverse events become imperative. Education of physicians for assessing individualized risk and providing optimal management of neurotoxicity is crucial to make CAR-T therapies safer and adoptable in clinical practice also in brain tumors.https://www.frontiersin.org/articles/10.3389/fonc.2023.1206983/fullCAR-T therapyneurotoxicitygliomaglioblastoma (GBM)immune effector cell-associated neurotoxicity syndrome (ICANS)ASTCT grading scale |
| spellingShingle | Lidia Gatto Ilaria Ricciotti Alicia Tosoni Vincenzo Di Nunno Stefania Bartolini Lucia Ranieri Enrico Franceschi CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap Frontiers in Oncology CAR-T therapy neurotoxicity glioma glioblastoma (GBM) immune effector cell-associated neurotoxicity syndrome (ICANS) ASTCT grading scale |
| title | CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap |
| title_full | CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap |
| title_fullStr | CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap |
| title_full_unstemmed | CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap |
| title_short | CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap |
| title_sort | car t cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in cns tumors fill the gap |
| topic | CAR-T therapy neurotoxicity glioma glioblastoma (GBM) immune effector cell-associated neurotoxicity syndrome (ICANS) ASTCT grading scale |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1206983/full |
| work_keys_str_mv | AT lidiagatto cartcellsneurotoxicityfromconsolidatedpracticeinhematologicalmalignanciestofledglingexperienceincnstumorsfillthegap AT ilariaricciotti cartcellsneurotoxicityfromconsolidatedpracticeinhematologicalmalignanciestofledglingexperienceincnstumorsfillthegap AT aliciatosoni cartcellsneurotoxicityfromconsolidatedpracticeinhematologicalmalignanciestofledglingexperienceincnstumorsfillthegap AT vincenzodinunno cartcellsneurotoxicityfromconsolidatedpracticeinhematologicalmalignanciestofledglingexperienceincnstumorsfillthegap AT stefaniabartolini cartcellsneurotoxicityfromconsolidatedpracticeinhematologicalmalignanciestofledglingexperienceincnstumorsfillthegap AT luciaranieri cartcellsneurotoxicityfromconsolidatedpracticeinhematologicalmalignanciestofledglingexperienceincnstumorsfillthegap AT enricofranceschi cartcellsneurotoxicityfromconsolidatedpracticeinhematologicalmalignanciestofledglingexperienceincnstumorsfillthegap |