4SCAR‐GD2‐modified T‐cell therapy in neuroblastoma with <i>MYCN</i> amplification: A case report with over 4‐year follow‐up data

Xu, Xinglian; Zhao, Wen; Yue, Zhixia; Qin, Maoquan; Jin, Mei; Chang, Lung‐Ji; Ma, Xiaoli

doi:10.1002/ped4.12181

Cited by 7 publications

(10 citation statements)

References 8 publications

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Section: Other Generations Of Car Structuresmentioning

confidence: 99%

“…This fourth-generation CAR exhibited higher tumor-killing activity than the third-generation CAR with a safety profile, leading to 4 years of survival of a neuroblastoma patient after fourth-generation CAR treatment [53]. Successful fourth-generation CAR T cells are being explored for the new era of treatment for neuroblastoma and other solid tumors.…”

Section: Other Generations Of Car Structuresmentioning

confidence: 99%

“…Although the second generation of CARs was mostly used in neuroblastoma clinical trials, the fourth generation of CARs has been developed. With neuroblastoma-targeted antigens incorporating multiple costimulatory molecules and a suicide gene-inducible caspase9 (iCasp9), the success of fourth-CAR T cells against MYCN amplification in neuroblastomas has been reported [ 53 ]. This fourth-generation CAR exhibited higher tumor-killing activity than the third-generation CAR with a safety profile, leading to 4 years of survival of a neuroblastoma patient after fourth-generation CAR treatment [ 53 ].…”

Section: Strategies To Improve Cars In Neuroblastomamentioning

confidence: 99%

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Strategies to Improve Chimeric Antigen Receptor Therapies for Neuroblastoma

et al. 2020

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Chimeric antigen receptors (CARs) are among the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastomas, the most common extracranial pediatric solid tumors with diverse characteristics, could be a promising candidate for using CAR therapies. Several methods harness CAR-modified cells in neuroblastoma to increase therapeutic efficiency, although the assessment has been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reasons behind the inadequate response against neuroblastoma of CAR-modified cells are still not well understood. It is essential to update the present state of comprehension of CARs to improve the efficiency of CAR therapies. This review summarizes the crucial features of CARs and their design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently being investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

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Section: Other Generations Of Car Structuresmentioning

confidence: 99%

Section: Other Generations Of Car Structuresmentioning

confidence: 99%

Section: Strategies To Improve Cars In Neuroblastomamentioning

confidence: 99%

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Strategies to Improve Chimeric Antigen Receptor Therapies for Neuroblastoma

et al. 2020

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“…Although the 2 nd generation of CARs is mostly used in neuroblastoma clinical trials, the 4 th generation CAR has been developed. With neuroblastoma-targeted antigen incorporated multiple costimulatory molecules and a suicide gene inducible caspase9 (iCasp9), the success of 4 th CAR T cells against MYCN amplification neuroblastoma has been reported [123]. This 4 th generation CAR exhibited higher tumor-killing activity than the 3 rd generation CAR with a safety profile, leading to 4 years survival of a neuroblastoma patient after 4 th generation CAR treatment [123].…”

Section: Others Generation Of Cars Structuresmentioning

confidence: 99%

“…With neuroblastoma-targeted antigen incorporated multiple costimulatory molecules and a suicide gene inducible caspase9 (iCasp9), the success of 4 th CAR T cells against MYCN amplification neuroblastoma has been reported [123]. This 4 th generation CAR exhibited higher tumor-killing activity than the 3 rd generation CAR with a safety profile, leading to 4 years survival of a neuroblastoma patient after 4 th generation CAR treatment [123]. Successful of this 4 th generation CAR T cells is explored to the new era treatment for neuroblastoma and other solid tumors.…”

Section: Others Generation Of Cars Structuresmentioning

confidence: 99%

Strategies to Improve Chimeric Antigen Receptors Therapies for Neuroblastoma

Sawaisorn¹,

Atjanasuppat²,

Anurathapan³

et al. 2020

Preprint

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Chimeric antigen receptors (CARs) is one of the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastoma, the most common extracranial pediatric solid tumors with diverse comportment, could be a promising candidate for using CARs therapies. Several methods harness CARs modified cells in neuroblastoma to increase therapeutic efficiency, albeit the assessment has still been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reason behind the inadequate response against neuroblastoma of CARs modified cells are still not well understood. It is essential to update the present reveal of comprehension of CARs to improve the efficiency of CARs therapies. This review summarizes the crucial features of CARs and its design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

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GD2-specific chimeric antigen receptor-modified T cells for the treatment of refractory and/or recurrent neuroblastoma in pediatric patients

Huang

Lin

et al. 2021

J Cancer Res Clin Oncol

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Purpose This study aimed to evaluate the safety and efficacy of chimeric antigen receptor (CAR) disialoganglioside 2 (GD2)-specific (4SCAR-GD2) T cells for treatment of refractory and/or recurrent neuroblastoma (NB) in pediatric patients. Experimental design A phase I clinical study using 4SCAR-GD2 T cells for the treatment of NB in pediatric patients was conducted. This study was registered at www.clinicaltrials.gov (NCT02765243). A lentiviral CAR with the signaling domains of CD28/4-1BB/CD3ζ-iCasp9 was transduced into activated T cells. The response to 4SCAR-GD2 T-cell treatment, and 4SCAR-GD2 T-cell expansion and persistence in patients were evaluated. Toxicities were determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Results Twelve patients were enrolled and finally ten patients were included in this clinical trial which started from January 1, 2016, to August 1, 2017. These patients had progressive disease (PD) before CAR T-cell infusion. After 4SCAR-GD2 T-cell treatment, 6 (6/10) had stable disease (SD) at 6 months, and 4 (4/10) remained SD at 1 year and alive after 3–4 years of follow-up. Six patients died due to disease progression by the end of July 1, 2020. The median overall survival (OS) time was 25 months (95% CI, 0.00–59.43), and the median progression-free survival (PFS) time was 8 months (95% CI, 0.25–15.75). Grade 3 or 4 hematological toxicities were the common adverse events frequently occurred after fludarabine and cyclophosphamide (Flu/cy) chemotherapy. Grade 1–2 toxicities such as cytokine release syndrome (CRS) and neuropathic pain were common, but were transient and mild. Conclusions The 4SCAR-GD2 T-cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.

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4SCAR‐GD2‐modified T‐cell therapy in neuroblastoma with MYCN amplification: A case report with over 4‐year follow‐up data

Cited by 7 publications

References 8 publications

Strategies to Improve Chimeric Antigen Receptor Therapies for Neuroblastoma

Strategies to Improve Chimeric Antigen Receptor Therapies for Neuroblastoma

Strategies to Improve Chimeric Antigen Receptors Therapies for Neuroblastoma

GD2-specific chimeric antigen receptor-modified T cells for the treatment of refractory and/or recurrent neuroblastoma in pediatric patients

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