Abstract：
BACKGROUND:Non-viral manufacturing of CAR T cells via the Sleeping Beauty transposon is cost effective and reduces the risk of insertional mutagenesis from viral transduction. However, the current gold standard methodology requires ex vivo numerical expansion of these cells on artificial antigen-presenting cells (AaPCs) for 4 weeks to generate CAR T cells of presumed sufficient quantity and function for clinical applications. METHOD:We engineered EGFRvIII-specific CAR T cells and monitored phenotypic changes throughout their ex vivo manufacturing. To reduce the culture time required to generate the CAR T-cell population, we selected for T cells in peripheral blood mononuclear cells prior to CAR modification (to eliminate the competing NK cell population). RESULTS:While we found increased expression of exhaustion markers (such as PD-1, PD-L1, TIM-3, and LAG-3) after 2 weeks in culture, whose levels continued to rise over time, we were able to generate a CAR+ T-cell population with comparable CAR expression and cell numbers in 2 weeks, thereby reducing manufacturing time by 50%, with lower expression of immune exhaustion markers. The CAR T cells manufactured at 2 weeks showed superior therapeutic efficacy in mice bearing established orthotopic EGFRvIII+ U87 gliomas. CONCLUSION:These findings demonstrate a novel, rapid method to generate CAR T cells by non-viral modification that results in CAR T cells superior in phenotype and function and further emphasizes that careful monitoring of CAR T-cell phenotype prior to infusion is critical for generating an optimal CAR T-cell product with full antitumor potential.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Caruso HG,Tanaka R,Liang J,Ling X,Sabbagh A,Henry VK,Collier TL,Heimberger ABdoi
10.1007/s11060-019-03311-ysubject
Has Abstractpub_date
2019-12-01 00:00:00pages
429-439issue
3eissn
0167-594Xissn
1573-7373pii
10.1007/s11060-019-03311-yjournal_volume
145pub_type
杂志文章abstract：PURPOSE:Most recent literature has confirmed the efficacy of single-session radiosurgery (sRS) in the treatment of intracranial meningioma. Unfortunately, sRS is not always applicable due to large tumor volume and the proximity of the tumor to critical structures. When sRS is not recommended, multi-session radiosurgery...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章,多中心研究
doi：10.1007/s11060-019-03196-x
更新日期：2019-07-01 00:00:00
abstract：:Successful management of a heavily pretreated 58-year-old woman with metastatic esthesioneuoblastoma using temozolomide is reported. There is no standard treatment of this tumors with extra- and intracranial manifestations. The response, long term stability and high quality of life using temozolomide for this tumor en...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1023/b:neon.0000040826.30636.4a
更新日期：2004-10-01 00:00:00
abstract：:After chromosome 22 and NF2 inactivation, the loss of chromosome 1p is one of the most frequent abnormalities encountered in meningiomas. However the putative tumor suppressor gene located on 1p inactivated in meningiomas has still to be identified. We screened 68 meningiomas for LOH on chromosome 22 and 1. We found 3...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1023/a:1006400723490
更新日期：2000-12-01 00:00:00
abstract：:Rapid first pass uptake of drugs is necessary to increase tissue deposition after intraarterial (IA) injection. Here we tested whether brain tissue deposition of a nanoparticulate liposomal carrier could be enhanced by coordinated manipulation of liposome surface charge and physiological parameters, such as IA injecti...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-014-1584-1
更新日期：2014-12-01 00:00:00
abstract：:Papillary meningioma is a rare subtype of meningioma that often behaves aggressively. In order to characterize factors that may influence this behavior, we chose to compare MIB-1 labeling index (LI) and telomerase RNA localization (hTR) in papillary meningiomas, meningiomas, and atypical meningiomas. LI is now often u...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1023/a:1006353322307
更新日期：1999-01-01 00:00:00
abstract：:Meningiomas in identical twins are extremely rare. To our knowledge, only one previous report of meningiomas in identical twins has been published. We present identical twin sisters with meningiomas. The tumors were located at a similar, but not a common, position (the cerebellopontine angle) in both twins. Histologic...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-009-0083-2
更新日期：2010-07-01 00:00:00
abstract：:Aberrant expression of stem cell-related genes in tumors may confer more primitive and aggressive traits affecting clinical outcome. Here, we investigated expression and prognostic value of the neural stem cell marker CD133, as well as of the pluripotency genes LIN28 and OCT4 in 37 samples of pediatric medulloblastoma...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-011-0647-9
更新日期：2012-01-01 00:00:00
abstract：:Intracranial Hodgkin's lymphoma (ICHL) in the HIV positive population is a rarely reported event with only three prior cases reported in the literature. In these prior reports, the outcome of the patients was uncertain or very poor. We report here the case of an HIV seropositive patient with an isolated intracranial r...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-008-9587-4
更新日期：2008-08-01 00:00:00
abstract：BACKGROUND:The role of immunotherapy for metastatic melanoma has expanded over the past decade triggering questions regarding the combination and timing of immunotherapy and radiation for brain metastases. We used the National Cancer Database (NCDB) to see if the time from radiation to immunotherapy in patients with me...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-020-03663-w
更新日期：2021-01-11 00:00:00
abstract：BACKGROUND:Elevated serum alkaline phosphatase has been previously studied as a biomarker for progression of metastatic disease and implicated in adverse skeletal events and worsened survival. The purpose of this study was to determine if serum alkaline phosphatase was a predictor of short-term mortality of patients un...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-018-2947-9
更新日期：2018-10-01 00:00:00
abstract：:Children with a brain tumor (BT) are at risk for a number of physical and cognitive problems that may lower their health-related quality of life (HRQoL). Executive functioning (EF) and intellectual ability are hypothesized to associate with HRQoL and deficits in these areas may be amenable to interventions. This study...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-016-2113-1
更新日期：2016-06-01 00:00:00
abstract：:The relation between hospital volume and outcomes for patients with glioblastoma is unknown. We undertook this study to determine the effect of hospital volume on treatment received and its effect on survival in patients with glioblastoma. We included patients from the National Cancer Database diagnosed with a gliobla...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-017-2598-2
更新日期：2017-12-01 00:00:00
abstract：:The growth pattern of pilocytic astrocytoma (PAs) is unpredictable. Gene expression profiling has recently demonstrated an inverse relationship between myelin basic protein (MBP) expression and progression free survival (PFS) in PAs. We present here the pattern of expression of oligodendroglial differentiation markers...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-007-9455-7
更新日期：2008-01-01 00:00:00
abstract：BACKGROUND:Despite aspirations to achieve equality in healthcare we know that socioeconomic differences exist and may affect treatment and patient outcome, also in serious diseases such as cancer. We investigated disparities in neurosurgical care and outcome for patients with low-grade glioma (LGG). METHODS:In this na...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-019-03378-7
更新日期：2020-01-01 00:00:00
abstract：:Boron neutron capture therapy (BNCT) is an experimental form of radiation therapy for malignant brain tumors and peripheral melanoma. The micro-distribution of the boron compound is critical to determine the radiation effects for both tumors and normal tissue. In the current dose calculation of BNCT, normal brain tiss...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-007-9494-0
更新日期：2008-03-01 00:00:00
abstract：:Degradation and remodelling of the extracellular matrix has been investigated, with the main focus on the balance between matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP). Recent reports disclose the presence of a novel MMP-inhibiting cell membrane-anchored glycoprotein designated 'rev...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-008-9606-5
更新日期：2008-09-01 00:00:00
abstract：:Ependymomas are glial neoplasms originating from the wall of the ventricles or from the spinal canal. The significance of histopathological features in accurately predicting biological behavior is still debated. Moreover, key molecular events in the pathogenesis of ependymoma are yet to be defined. The main objective ...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-009-0039-6
更新日期：2010-05-01 00:00:00
abstract：:Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PW...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-016-2300-0
更新日期：2017-01-01 00:00:00
abstract：:Identification of patients suffering from elevated psychosocial distress, the sources of the distress, and the necessary treatment of the distress can be rather difficult within the neurosurgical setting (e.g., lack of time, cognitive or aphasic disorders of the patients). The distress thermometer (DT) is a single-ite...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-010-0501-5
更新日期：2011-08-01 00:00:00
abstract：:We describe the case of a young man presenting with an extra-nodal, intramedullary non-Hodgkin's lymphoma of the cervical spinal cord. This is a very uncommon presentation of this neoplasm. The patient was treated with craniospinal radiotherapy, with survival for two and a half years before death from recurrent diseas...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/BF01059959
更新日期：1995-01-01 00:00:00
abstract：:Chordoid is a rare variant of meningioma that displays a high recurrence rate. In this study we evaluated the immunohistochemical expression of factors that regulate the neo-angiogenesis process in a case of chordoid meningioma with an adverse clinical course. A high microvessel density (MVD), as well as high VEGF and...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-009-9942-0
更新日期：2009-12-01 00:00:00
abstract：:Glioblastoma Multiforme frequently metastasises from their original location by for example infiltration along white matter tracts [1]. GBM metastasis outside the central nervous system is distinctly rare though there are previous reports of spread to various organs [2-5]. We add an unusual case of a patient with aggr...
journal_title：Journal of neuro-oncology
pub_type： 信件
doi：10.1007/s11060-005-1480-9
更新日期：2005-09-01 00:00:00
abstract：:In the human glioblastoma cell line, T-MG1, plasminogen activator activity (PA-activity) was demonstrated by using the chromogenic substrate S-2251. Using monoclonal antibodies against human urokinase type PA (u-PA) and human tissue type PA (t-PA), only u-PA activity was found in T-MG1 cell extracts. The u-PA activity...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/BF00163713
更新日期：1988-11-01 00:00:00
abstract：PURPOSE:This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. EXPERIMENTAL DESIGN:Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentori...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1007/s11060-018-2831-7
更新日期：2018-07-01 00:00:00
abstract：:Patients with metastatic well-differentiated thyroid cancer have a generally favorable long-term outcome although multi-organ involvement is a known marker of poor prognosis. Brain metastases are rare, occurring in less than 1% of patients with thyroid cancer. Few patients have been managed with stereotactic radiosurg...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章,多中心研究
doi：10.1007/s11060-010-0175-z
更新日期：2010-06-01 00:00:00
abstract：:Optimal treatment of anaplastic oligodendroglial tumors (AOT) in elderly patients is debatable. We report a retrospective study of 44 consecutive patients aged 70 years or older [median age: 74 years; median Karnofsky performance status (KPS): 70] treated with up-front chemotherapy using temozolomide (TMZ) at conventi...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-010-0264-z
更新日期：2011-02-01 00:00:00
abstract：PURPOSE:The poor results from treatment of high grade glioma prompted us to explore new protocols involving concurrent radio-chemotherapy. Our primary objective was to evaluate the feasibility of very early postoperative chemotherapy with BCNU, concurrent radio-chemotherapy with carboplatin and teniposide, and post-rad...
journal_title：Journal of neuro-oncology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00177276
更新日期：1996-12-01 00:00:00
abstract：INTRODUCTION:The standard treatment for primary central nervous system lymphoma (PCNSL) involves induction methotrexate-based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). As WBRT carries a substantial risk for cognitive impairment, alternative consolidation treatments have been used to re...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-019-03257-1
更新日期：2019-09-01 00:00:00
abstract：:Serious dermatologic adverse events such as erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported in patients receiving antiepileptic drugs (AEDs) and cranial radiotherapy (RT). Given the frequency of AED-associated rashes and the infrequency of serious dermatolo...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-014-1457-7
更新日期：2014-08-01 00:00:00
abstract：:Thirty-one patients with metastatic brain tumors that either failed to respond or recurred after conventional therapy were treated by intra-arterial infusion of 100 mg/m2 of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) into either a carotid or vertebral artery. Five patients (three with lung cancer, one with breast can...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/BF00165605
更新日期：1983-01-01 00:00:00
