Locoregional CAR T cells for children with CNS tumors: Clinical procedure and catheter safety

Vitanza, Nicholas A.; Ronsley, Rebecca; Choe, Michelle; Henson, Casey; Breedt, Mandy; Barrios-Anderson, Adriel; Wein, Amy; Brown, Christopher; Beebe, Adam; Kong, Ada; Kirkey, Danielle; Lee, Brittany M.; Leary, Sarah; Crotty, Erin; Hoeppner, Corrine; Holtzclaw, Susan; Wilson, Ashley; Gustafson, Joshua A.; Foster, Jessica; Iliff, Jeffrey J.; Goldstein, Hannah; Browd, Samuel R.; Lee, Amy; Ojemann, Jeffrey G.; Pinto, Navin; Gust, Juliane; Gardner, Rebecca; Jensen, Michael C.; Hauptman, Jason S.; Park, Julie R.

doi:10.1016/j.neo.2022.100870

Cited by 15 publications

(7 citation statements)

References 35 publications

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“…No fatal or life-threatening toxicities were observed, but fever and tachycardia were common adverse events, which might represent systemic effects despite localized delivery (reviewed in [ 95 ]). Locoregional delivery of CAR-T cells was not only tested in adults but also in children with CNS tumors [ 96 , 97 , 98 ]. On the other hand, the intracranial approach requires an invasive procedure and can be associated with certain complications (e.g., infection and bleeding).…”

Section: Discussionmentioning

confidence: 99%

Chimeric Antigen Receptor T Cells in Glioblastoma—Current Concepts and Promising Future

Kringel

Lamszus

Mohme

2023

Cells

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Glioblastoma (GBM) is a highly aggressive primary brain tumor that is largely refractory to treatment and, therefore, invariably relapses. GBM patients have a median overall survival of 15 months and, given this devastating prognosis, there is a high need for therapy improvement. One of the therapeutic approaches currently tested in GBM is chimeric antigen receptor (CAR)-T cell therapy. CAR-T cells are genetically altered T cells that are redirected to eliminate tumor cells in a highly specific manner. There are several challenges to CAR-T cell therapy in solid tumors such as GBM, including restricted trafficking and penetration of tumor tissue, a highly immunosuppressive tumor microenvironment (TME), as well as heterogeneous antigen expression and antigen loss. In addition, CAR-T cells have limitations concerning safety, toxicity, and the manufacturing process. To date, CAR-T cells directed against several target antigens in GBM including interleukin-13 receptor alpha 2 (IL-13Rα2), epidermal growth factor receptor variant III (EGFRvIII), human epidermal growth factor receptor 2 (HER2), and ephrin type-A receptor 2 (EphA2) have been tested in preclinical and clinical studies. These studies demonstrated that CAR-T cell therapy is a feasible option in GBM with at least transient responses and acceptable adverse effects. Further improvements in CAR-T cells regarding their efficacy, flexibility, and safety could render them a promising therapy option in GBM.

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Section: Discussionmentioning

confidence: 99%

Chimeric Antigen Receptor T Cells in Glioblastoma—Current Concepts and Promising Future

Kringel

Lamszus

Mohme

2023

Cells

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“…Intensive research has centered on developing diverse protein-based logic-circuit strategies to enhance the specificity of CAR T cell activation and cytotoxicity towards tumor cells ( 83 – 85 ). Additionally, locoregional administration of CAR T cells, aimed at concentrating antitumor activity within the tumor microenvironment, may offer a potential solution to mitigate off-tumor toxicity ( 86 – 88 ).…”

Section: Achilles Heels Of Car T-cell Therapymentioning

confidence: 99%

Charting new paradigms for CAR-T cell therapy beyond current Achilles heels

Li,

Hu,

et al. 2024

Front. Immunol.

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Chimeric antigen receptor-T (CAR-T) cell therapy has made remarkable strides in treating hematological malignancies. However, the widespread adoption of CAR-T cell therapy is hindered by several challenges. These include concerns about the long-term and complex manufacturing process, as well as efficacy factors such as tumor antigen escape, CAR-T cell exhaustion, and the immunosuppressive tumor microenvironment. Additionally, safety issues like the risk of secondary cancers post-treatment, on-target off-tumor toxicity, and immune effector responses triggered by CAR-T cells are significant considerations. To address these obstacles, researchers have explored various strategies, including allogeneic universal CAR-T cell development, infusion of non-activated quiescent T cells within a 24-hour period, and in vivo induction of CAR-T cells. This review comprehensively examines the clinical challenges of CAR-T cell therapy and outlines strategies to overcome them, aiming to chart pathways beyond its current Achilles heels.

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“…Chemokine receptor expression in CAR-T cells [134,[138][139][140][141]. Loco-regional delivery of CAR-T cells [134,138,[142][143][144][145].…”

Section: Challenges Potential Solutionsmentioning

confidence: 99%

Glioblastoma Vaccines as Promising Immune-Therapeutics: Challenges and Current Status

Squalli Houssaini,

Lamrabet,

Nshizirungu

et al. 2024

Vaccines

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Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard treatments including surgical resection, radiotherapy, and chemotherapy, have failed to significantly improve the prognosis of glioblastoma patients. Currently, immunotherapeutic approaches based on vaccines, chimeric antigen-receptor T-cells, checkpoint inhibitors, and oncolytic virotherapy are showing promising results in clinical trials. The combination of different immunotherapeutic approaches is proving satisfactory and promising. In view of the challenges of immunotherapy and the resistance of glioblastomas, the treatment of these tumors requires further efforts. In this review, we explore the obstacles that potentially influence the efficacy of the response to immunotherapy and that should be taken into account in clinical trials. This article provides a comprehensive review of vaccine therapy for glioblastoma. In addition, we identify the main biomarkers, including isocitrate dehydrogenase, epidermal growth factor receptor, and telomerase reverse transcriptase, known as potential immunotherapeutic targets in glioblastoma, as well as the current status of clinical trials. This paper also lists proposed solutions to overcome the obstacles facing immunotherapy in glioblastomas.

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Locoregional CAR T cells for children with CNS tumors: Clinical procedure and catheter safety

Cited by 15 publications

References 35 publications

Chimeric Antigen Receptor T Cells in Glioblastoma—Current Concepts and Promising Future

Chimeric Antigen Receptor T Cells in Glioblastoma—Current Concepts and Promising Future

Charting new paradigms for CAR-T cell therapy beyond current Achilles heels

Glioblastoma Vaccines as Promising Immune-Therapeutics: Challenges and Current Status

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