Real-world data of clazosentan in combination therapy for aneurysmal subarachnoid hemorrhage: a multicenter retrospective cohort study.

Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm, significantly associated with morbidity and mortality. In double-blind, placebo-controlled phase 3 studies, clazosentan reduces cerebral vasospasm-related morbidity and all-cause mortality in patients with aSAH. There are no reports about the clinical efficacy of clazosentan combination therapy with some other drugs. Initially, we explored the efficacy of clazosentan combination therapy with cilostazol, statin, and antiepileptic drugs. Subsequently, we assessed the add-on effect of fasudil to clazosentan combination therapy for aSAH patients. This multicenter, retrospective, observational cohort study included Japanese patients with aSAH between June 2022 and March 2023. The primary outcome was the ordinal score on the modified Rankin Scale (mRS; range, 0-6, with elevated scores indicating greater disability) at discharge. Among the 47 cases (women 74.5%; age 64.4 ± 15.0 years) undergoing clazosentan combination therapy, 29 (61.7%) resulted in favorable outcomes. Overall, vasospasm occurred in 16 cases (34.0%), with four cases (8.5%) developing vasospasm-related delayed cerebral ischemia (DCI). Both hypotension and vasospasm-related DCI were related to unfavorable outcome at discharge. Fasudil were added in 18 (38.3%) cases. Despite adding fasudil to clazosentan combination therapy, the incidence of aSAH-related vasospasm did not decrease. Added-on fasudil to combination therapy related to pulmonary edema, vasospasm, and vasospasm-related DCI, and unfavorable outcomes. Clazosentan combination therapy could potentially result in favorable outcomes for aSAH patients to prevent post-aSAH vasospasm-related DCI. The add-on effect of fasudil to combination therapy did not demonstrate a significant impact in reducing aSAH-related vasospasm or improving outcomes at discharge.

Suitability of a 7-F ExoSeal Vascular Closure Device for Femoral Artery Punctures Made by 8-F or 9-F Introducer Sheaths.

PURPOSE: To establish the safety and efficacy of the 7-F ExoSeal device for the closure of femoral puncture sites made by 8-F or 9-F introducer sheaths. METHODS: Between January 2013 and December 2016, 332 patients (mean age 68.4±12.1 years; 195 men) underwent neurointerventional procedures via percutaneous puncture of the common femoral artery and an 8-F (n=272, 81.9%) or 9-F (n=60, 18.1%) introducer. The access sites were sealed with a 7-F ExoSeal in all cases. Procedure success and closure-related complication rates were evaluated, and risk factors for complications were analyzed by comparing patient characteristics between those who did and did not experience complications. RESULTS: Procedure success rates were 99.3% in the 8-F group and 100% in the 9-F group. The overall complication rate was 6.3% (n=17; all in the 8-F group), of which 13 (4.8%) were minor sequelae, including access-site hematoma (n=8), oozing (n=3), pseudoaneurysm (n=1), and retroperitoneal bleeding (n=1). Among the 4 (1.5%) major complications were 3 instances of bleeding requiring a blood transfusion and 1 surgical vascular repair. No complications were observed in the 9-F group. Patients who experienced complications had significantly longer activated clotting times (262±46 vs 218±55 seconds; p<0.001) compared with patients without complications. CONCLUSION: A 7-F ExoSeal vascular closure device is safe and effective for the closure of femoral puncture sites made by 8-F or 9-F introducer sheaths.

Crevice sign as an indicator of plaque laceration associated with postoperative severe thromboembolism after carotid artery stenting: a case report.

Carotid artery stenting (CAS) is increasingly utilized in patients with carotid artery stenosis. Various intraprocedural and postprocedural complications have been reported in the literature. We present a case of symptomatic major thromboembolism after CAS. The intraprocedural angiogram showed extraordinary slow filling of the contrast medium into the plaque, which we named as "crevice sign." An 83-year-old man presented repeat right amaurosis fugax for 6 months. The radiological examinations revealed 85% stenosis of the origin of the right internal carotid artery. The patient underwent right CAS. The procedure was performed without any problems; however, the angiogram showed slow filling of contrast medium into the carotid plaque through the stent (crevice sign). Sixty minutes later in the ward, the patient presented sudden onset of left hemiparesis and aphasia. Emergency catheter angiography did not show in-stent thrombus, major artery occlusion, or the crevice sign. Magnetic resonance imaging on the next day revealed wide acute infarction of the right cerebral hemisphere. Physicians should be aware of the intraprocedural crevice sign so that a subsequent catastrophic ischemic event can be prevented.

Successful steroid treatment of coma induced by severe spontaneous intracranial hypotension.

Spontaneous intracranial hypotension (SIH) is a syndrome characterized by low cerebrospinal fluid (CSF) pressure and postural headaches. It is a rare condition which may sometimes present with severe symptoms such as stupor or coma. The standard treatment protocol includes conservative measures such as bed rest, hydration, and steroids. However, severe cases may require invasive measures such as epidural blood patch (EBP), continuous epidural saline infusion, epidural fibrin glue, or surgical repair of the dural defect. In this report, we describe a case of severe SIH resulting in coma that exhibited dramatic improvement on intravenous administration of steroids. This is the first report of severe SIH causing coma that was treated non-invasively by steroids only.

Overlap stenting for in-stent restenosis after carotid artery stenting.

Our aim was to assess the clinical safety and efficacy of overlap stenting for in-stent restenosis after carotid artery stenting. The study was conducted between July 2008 and February 2015. A database of consecutive carotid artery stenting procedures was retrospectively assessed to identify the cases of in-stent restenosis that were treated with overlap stenting under proximal or distal protection. The clinical and radiological records of the patients were then reviewed. Of the 155 CAS procedures in 149 patients from the database, 6 patients met the inclusion criteria. All the 6 patients were initially treated with moderate dilatation because of the presence of an unstable plaque. The technical success rate of the overlap stenting was 100%, with no 30-day mortality or morbidity. In addition, there was no further in-stent restenosis during a follow-up period of over 12 months. These results indicated that overlap stenting for in-stent restenosis after carotid artery stenting was both safe and effective in our cohort.

Treatment protocol based on assessment of clot quality during endovascular thrombectomy for acute ischemic stroke using the Trevo stent retriever.

The optional endovascular approach for acute ischemic stroke is unclear. The Trevo stent retriever can be used as first-line treatment for fast mechanical recanalization. The authors developed a treatment protocol for acute ischemic stroke based on the assessment of clot quality during clot removal with the Trevo. This prospective single-center study included all patients admitted for acute ischemic stroke between July 2014 and February 2015, who underwent emergency endovascular treatment. According to the protocol, the Trevo was used for first-line treatment. Immediately after the Trevo was deployed, the stent delivery wire was pushed to open the stent by force (ACAPT technique). Clot quality was assessed on the basis of the perfusion status after deployment of the Trevo; continued occlusion or immediate reopening either reoccluded or maintained after the stent retriever had been in place for 5 min. If there was no obvious clot removal after the first pass with the Trevo, according to the quality of the clot, either a second pass was performed or another endovascular device was selected. Twelve consecutive patients with acute major cerebral artery occlusion were analyzed. Thrombolysis in cerebral infarction score 2b and 3 was achieved in 11 patients (91.7%) and 9 (75%) had a good clinical outcome after 90 days based on a modified Rankin scale score ≤ 2. Symptomatic intracranial hemorrhage occurred in 1 patient (8.3%). The overall mortality rate was 8.3%. Endovascular thrombectomy using the Trevo stent retriever for first-line treatment is feasible and effective.

[A Novel, Less Invasive Protection Method for Carotid Artery Stenting].

Purpose: We present a novel, less invasive protection method for carotid artery stenting. Case presentation: A 67-year-old man presented with symptomatic severe left carotid artery stenosis. A transfemoral approach was dangerous because of an abdominal aortic aneurysm. A 6Fr Axcelguide Simmonds catheter was inserted into the right brachial artery, and advanced into the left common carotid artery. Next, a 6Fr Optimo 100-cm catheter was coaxially navigated into the left common carotid artery. A PercuSurge GuardWire 300-cm was coaxially navigated into the left external carotid artery. Under flow reversal with the 2 balloons, another PercuSurge GuardWire 300-cm was navigated into the distal left internal carotid artery through the lesion. After both PercuSurge GuardWire balloons were inflated, the 6Fr Optimo was deflated and retrieved using a catheter exchange technique. Then, under distal double-balloon protection, routine stenting was performed. Conclusions: This technique is safer and less invasive than previous methods, especially in cases with difficult femoral access and vulnerable carotid plaque.

Preoperative embolization of meningiomas with low-concentration n-butyl cyanoacrylate.

The aim of this study was to determine the clinical safety and efficacy of preoperative embolization of meningiomas with low-concentration n-butyl cyanoacrylate (NBCA). Nineteen cases of hypervascular intracranial meningiomas were treated by preoperative embolization with 14% NBCA, using a wedged superselective catheterization of feeding arteries and reflux-hold-reinjection technique. Clinical data of the patients and radiological and intra-surgical findings were reviewed. All tumors were successfully devascularized without any neurological complications. Marked reduction of tumor staining with extensive NBCA penetration was achieved in 13 cases. Perioperative blood transfusion was only required in two cases. These results indicate that preoperative embolization of meningiomas with low-concentration NBCA is both safe and effective.

A case of ruptured intrameatal aneurysm successfully treated with coil embolization.

Aneurysms within the internal acoustic canal are rare. We report the case of a 71-year-old female with subarachnoid hemorrhage resulting from a ruptured distal anterior inferior cerebellar artery which was not detected on initial radiological examination. A second rupture was detected by contrast-enhanced computed tomography and successfully treated by endovascular coil embolization. The patient recovered without neurological deficits. To the best of our knowledge, this is the first report of an intrameatal aneurysm treated by endovascular coil embolization. We suggest endovascular coil embolization as an alternative to open surgery, even in cases of deep intrameatal aneurysm.

[A Case of Cavernous Sinus Dural Arteriovenous Fistula after Transverse-Sigmoid Sinus Dural Arteriovenous Fistula Treatment with Radical Transvenous Coil Embolization].

PURPOSE: We report a case of cavernous sinus dural arteriovenous fistula (dAVF) that developed after the treatment of a transverse-sigmoid sinus dAVF using transvenous embolization (TVE). CASE PRESENTATION: A 72-year-old woman presented with headache and left-sided tinnitus. Angiography demonstrated the presence of a left transverse-sigmoid sinus dAVF. After TVE, the patient's symptoms completely disappeared. Three years later, she complained of left-sided tinnitus and diplopia, and angiography revealed the presence of a left cavernous sinus dAVF. We performed transvenous coil embolization, and the dAVF disappeared. CONCLUSIONS: TVE has been widely recognized as an effective treatment for dAVF. However, dAVF may develop at a different location after TVE in a few cases. A long-term follow-up is therefore recommended.

[Case of an anterior communicating artery aneurysm with acute in-stent occlusion during coil embolization].

PURPOSE: We report a case of acute in-stent occlusion during a stent-assisted coil embolization of a communicating artery aneurysm. CASE PRESENTATION: A 58-year-old man presented with a regrowth of an anterior communicating artery aneurysm one year after the initial coil embolization. An acute in-stent occlusion occurred during coil filling through the stent strut. We performed a successful recanalization of the stent using antithrombotic agents. CONCLUSIONS: Acute in-stent occlusion is a possible complication of stent-assisted coil embolization of aneurysms, particularly in narrow parent arteries. Our patient was recovered using antithrombotic drugs and did not present any major ischemic symptoms.

A Case of Recurrence of Benign Convexity Primary Intraosseous Meningioma.

Meningiomas originating within the bones of the skull are rare and have been reported as primary intraosseous meningiomas (PIOM). Moreover, PIOMs with a skull base location or malignant pathology are predisposed to recurrence; however, recurrence is quite rare among PIOMs characterized by a convexity location and benign pathology. Here, we present a case of extensive recurrence of a convex intraosseous meningioma with benign pathology. A 72-year-old woman presented with a headache to our hospital. Gd contrast-enhanced magnetic resonance imaging revealed an enhanced tumor in the left frontal to the parietal region extending through the calvarial bone and invading the subdural space and subcutaneous tissue. Skull radiograph and computed tomography identified a remarkable osteolytic change in the lesion. Macroscopic complete resection (MCR) of the tumor and the surrounding tissues was performed. The tumor was histopathologically diagnosed as a transitional meningioma (World Health Organization grade 1). Seven years after the surgery, the patient presented with dysarthria, and the recurrence of the tumor was identified as massive lesions extending through the calvarial bone to the orbital bone, partially protruding into the brain and scalp. MCR was performed again, with the reconstruction of the skull for an extensive calvarial area using a titanium plate. This case is unique due to the extensiveness of the recurrent tumor and its rarity. Here, we report the details of the clinical course and discuss the characteristics of this case.

Efficacy of intraoperative irrigation with artificial cerebrospinal fluid in chronic subdural hematoma surgery: study protocol for a multicenter randomized controlled trial.

BACKGROUND: The surgical techniques for treatment of chronic subdural hematoma (CSDH), a common neurosurgical condition, have been discussed in a lot of clinical literature. However, the recurrence proportion after CSDH surgery remains high, ranging from 10 to 20%. The standard surgical procedure for CSDH involves a craniostomy to evacuate the hematoma, but irrigating the hematoma cavity during the procedure is debatable. The authors hypothesized that the choice of irrigation fluid might be a key factor affecting the outcomes of surgery. This multicenter randomized controlled trial aims to investigate whether intraoperative irrigation using artificial cerebrospinal fluid (ACF) followed by the placement of a subdural drain would yield superior results compared to the placement of a subdural drain alone for CSDH. METHODS: The study will be conducted across 19 neurosurgical departments in Japan. The 1186 eligible patients will be randomly allocated to two groups: irrigation using ACF or not. In either group, a subdural drain is to be placed for at least 12 h postoperatively. Similar to what was done in previous studies, we set the proportion of patients that meet the criteria for ipsilateral reoperation at 7% in the irrigation group and 12% in the non-irrigation group. The primary endpoint is the proportion of patients who meet the criteria for ipsilateral reoperation within 6 months of surgery (clinical worsening of symptoms and increased hematoma on imaging compared with the postoperative state). The secondary endpoints are the proportion of reoperations within 6 months, the proportion being stratified by preoperative hematoma architecture by computed tomography (CT) scan, neurological symptoms, patient condition, mortality at 6 months, complications associated with surgery, length of hospital stay from surgery to discharge, and time of the surgical procedure. DISCUSSION: We present the study protocol for a multicenter randomized controlled trial to investigate our hypothesis that intraoperative irrigation with ACF reduces the recurrence proportion after the removal of chronic subdural hematomas compared with no irrigation. TRIAL REGISTRATION: ClinicalTrials.gov jRCT1041220124. Registered on January 13, 2023.

Peptide-pulsed dendritic cell vaccination targeting interleukin-13 receptor α2 chain in recurrent malignant glioma patients with HLA-A*24/A*02 allele.

BACKGROUND AIMS: Dendritic cell (DC)-based vaccination targeting tumor-associated antigens is an attractive approach to overcoming the limitations of current treatments for malignant gliomas (MG). Interleukin-13 receptor α2 chain (IL-13Rα2) is a promising target because of its abundant and specific expression in MG. We conducted a phase I trial of DC vaccination in patients with recurrent MG using two IL-13Rα2-derived peptides restricted to HLA-A*0201 and -A*2402. The objective was to evaluate the safety and clinical and immunologic responses. METHODS: Eight recurrent MG patients were enrolled. DC were generated from peripheral blood and pulsed with HLA-matched peptide; 1 × 10(7) DC were administered every 2 weeks for a maximum of six immunizations. The T-cell response in peripheral blood was evaluated by tetramer and ELISPOT assays in HLA-A*2402 patients. RESULTS: All enrolled patients except one completed at least four DC vaccinations. No severe adverse events were observed. A positive T-cell response was detected in two out of three evaluable HLA-A*2402 patients. One patient achieved stable disease for 16 months and another patient showed a dramatic regression for one lesion for 4 months. CONCLUSIONS: The regimen was feasible and safe, and the HLA-A*24-restricted peptide exhibited a capacity to induce immune responses. These results warrant further studies to evaluate whether add-on regimens to post-operative chemoradiotherapy delays recurrence in newly diagnosed MG patients.

Profound tumor-specific Th2 bias in patients with malignant glioma.

BACKGROUND: Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4+ helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4+ helper T cell responses in the peripheral blood of patients with malignant gliomas. METHODS: Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM) (n = 8), recurrent GBM (n = 5), meningioma (n = 7), and healthy controls (n = 6) with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb) and an immunodominant peptide epitope derived from myelin basic protein (MBP) serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias. RESULTS: We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs. CONCLUSIONS: Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically.

A Case of Primary Leptomeningeal Lymphoma Presenting with Hydrocephalus Characterized by Disproportionately Large Fourth Ventricle.

Primary leptomeningeal malignant lymphoma (PLML) is a rare variant of primary central nerve system malignant lymphoma (PCNSL) which is restricted to leptomeninges. The lesions of PLML can often be detected as abnormal enhancement on the surface of central nervous system or the ventricular wall on magnetic resonance imaging (MRIs). Cerebrospinal fluid (CSF) evaluation together with such MRI findings provides the definitive diagnosis of PLML. Here, we present a 45-year-old female case of PLML in which hydrocephalus with disproportionately large fourth ventricle was observed at presentation with gait instability. Head MRI revealed no abnormal enhancement and CSF cytology was negative, leaving the cause of hydrocephalus undetermined. Endoscopic third ventriculostomy (ETV) was effectively performed for hydrocephalus and her symptoms disappeared. Nearly 2 years later, she was brought to emergent room due to unconsciousness with the recurrence of hydrocephalus. MRI showed expanded fourth ventricle and abnormal enhancement on the ventricular wall. The endoscopic surgery for improving CSF flow was successful and inflammatory change was endoscopically observed on the ventricular wall involving aqueduct. Pathological diagnosis of the specimen from the ventricular wall proved B-cell lymphoma. Because neither brain parenchymal masses nor systemic tumors were identified, she was diagnosed with PLML and treated by high-dose methotrexate. She was in a stable state 2 years after the diagnosis of PLML. We report and discuss the characteristics of this case.

Malignant Glioma in the Cerebellum Presenting as Multiple Small Lesions.

Malignant glioma, the most common malignant primary brain tumor in adults, usually occurs in supratentorial space as a single mass lesion, and cerebellar location and multiple appearance are uncommon. We report a case of a 69-year-old female with three lesions simultaneously found in the cerebellum on magnetic resonance images (MRIs) after suffering from gait disturbance. Two lesions were around 15 mm in size and the other one was observed as a spotty enhancement. Although MRI findings suggested brain metastases, whole body examinations denied any primary malignancies. Biopsy for one lesion in the cerebellum was performed, which resulted in pathological diagnosis of malignant astrocytoma. The lesions were considered multicentric glioma based on MRI definition. The treatment with temozolomide and whole brain radiation was completed. Although the patient was discharged in an independent state with the shrinkage of the tumors, she unexpectedly died following sudden loss of consciousness from an unknown cause one month after discharge. The coincidence of cerebellar location and multicentricity characterized by smallness is quite rare in glioma patients, and such MRI findings might be misleading for the diagnosis. We describe the details of the case and discuss the pathogenesis of this unique presentation of malignant glioma with the literatures.

The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma.

Cancer/testis antigens (CTAs) are considered to be suitable targets for the immunotherapy of human malignancies. It has been demonstrated that in a variety of tumors, the expression of certain CTAs is activated via the demethylation of their promoter CpG islands. In our study, we have shown that while the composite expression of 13 CTAs in 30 human glioma specimens and newly established cell lines from the Japanese population was nearly imperceptible, the DNA-demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) markedly reactivated CTA expression in glioma cells but not in normal human cells. We quantified the diminished methylation status of NY-ESO-1-one of the most immunogenic CTAs-following 5-aza-CdR treatment by using a novel Pyrosequencing technology and methylation-specific PCR. Microarray analysis revealed that 5-aza-CdR is capable of signaling the immune system, particularly, human leukocyte antigen (HLA) class I upregulation. (51)Cr-release cytotoxicity assays and cold target inhibition assays using NY-ESO-1-specific cytotoxic T lymphocyte (CTL) lines demonstrated the presentation of de novo NY-ESO-1 antigenic peptides on the cell surfaces. In an orthotopic xenograft model, the systemic administration of 5-aza-CdR resulted in a significant volume reduction of the transplanted tumors and prolonged the survival of the animals after the adoptive transfer of NY-ESO-1-specific CTLs. These results suggested that 5-aza-CdR induces the expression of epigenetically silenced CTAs in poorly immunogenic gliomas and thereby presents a new strategy for tumor immunotherapy targeting 5-aza-CdR-induced CTAs.

A combination of IFN-beta and temozolomide in human glioma xenograft models: implication of p53-mediated MGMT downregulation.

PURPOSE: Methylation of the O(6)-methyguanine-DNA methyltransferase (MGMT) gene promoter in gliomas has been reported to be a useful predictor of the responsiveness to temozolomide (TMZ). In our previous experiments, we observed that IFN-beta sensitized TMZ-resistant glioma cells with the unmethylated MGMT promoter and that the mechanism of action was possibly due to attenuation of MGMT expression via induction of TP53. In this study, (1) we explored the synergistic effect of IFN-beta and TMZ in the animal model, and (2) clarified the role of IFN-beta induced TP53 in the human MGMT promoter. METHODS: (1) Nude mice with either subcutaneous T98 (TMZ-resistant) or U251SP (TMZ-sensitive) tumor were treated with IFN-beta/TMZ for 5 consecutive days. (2) The MGMT promoter activity was assayed by a luciferase reporter system in Saos2 (p53-null) cells transduced with a p53-adenoviral vector, and T98 glioma cells treated with IFN-beta. RESULTS: (1) A combination of IFN-beta/TMZ had significant synergistic antitumor activity on the growth of both T98 and U251SP tumors. (2) MGMT promoter activity was suppressed by either adenovirally transduced p53 or IFN-beta. CONCLUSIONS: It would be appealing to consider a prospective clinical trial in which genetic markers are used for personalized drug selection, eliciting other forms of treatment or inhibition of MGMT for those with MGMT expression. In this context, IFN-beta inactivates MGMT via p53 gene induction and enhances the therapeutic efficacy to TMZ.

Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor alpha2 chain, a glioma-associated antigen.

OBJECT: The human leukocyte antigen-A24 (HLA-A24) allele is highly expressed in Asians. This allele is expressed in 60% of the Japanese population and in a significant number of people of other ethnicities. The interleukin-13 type alpha2 receptor (IL-13Ralpha2) has been shown to be a glioma-specific antigen, and is abundantly expressed in a majority of high-grade astrocytomas. In this study, the authors first investigated the suitability of IL-13Ralpha2 as a target antigen of malignant glioma cells, and then identified a potential HLA-A24-restricted peptide derived from IL-13Ralpha2. METHODS: The expression of IL-13Ralpha2 in glioma tissues was examined by reverse transcription-polymerase chain reaction analysis. To identify the desired epitope, the authors selected 5 candidate peptides from IL-13Ralpha2 that were predicted to bind to HLA-A24. The lytic activity of cytotoxic T lymphocytes (CTLs) induced by peptide-pulsed dendritic cells was analyzed against various glioma cell lines and freshly isolated human glioma cells. RESULTS: In a series of glioma tissues obtained in 29 patients, the authors found that > 50% of high-grade gliomas expressed IL-13Ralpha2. Of the 5 peptides tested, P174 (WYEGLDHAL) was found to be the most useful for the induction of HLA-A24-restricted and IL-13Ralpha2-specific CTLs. A CTL line induced by P174 also showed antigen-specific cytotoxicity to surgically removed glioma cells depending on their level of expression of IL-13Ralpha2 and HLA-A24. CONCLUSIONS: Interleukin-13Ralpha2 is a glioma-specific antigen, and the immunogenic peptide P174 may contribute to a peptide-based immunotherapy against malignant glioma cells expressing HLA-A24.