Heon Yoo

Purpose:This single-center, open-label, phase I trial evaluated the safety and tolerability of chimeric antigen receptor (CAR) T cells targeting interleukin 13 receptor α2 (IL13Rα2) in patients with malignant gliomas. Patients and Methods:Adults with World Health Organization grade 3 to 4 gliomas, recurrent after standard treatment and expressing IL13Rα2 (confirmed by immunohistochemistry), received a single intravenous infusion of autologous CAR T cells. Primary objectives were to measure the maximum tolerated dose (MTD) and recommended phase II dose. Secondary objectives included assessment of pharmacokinetics, objective response rate, progression-free survival (PFS), and overall survival (OS). Results:Ten patients were sequentially assigned to 3 dosing cohorts (1 × 107, 3 × 107, and 1 × 108 cells/kg). The MTD was not reached, as no dose-limiting toxicities were observed, and all adverse events (AE) were grade ≤3 without irreversible sequelae. The most common treatment-related AE were pyrexia (70%) and elevated transaminase (70%). CAR T-cell levels in blood reached peak concentrations at a median of 7 days (range, 3–14), and the transgene was detected in cerebrospinal fluid from 5 of 6 patients treated at the higher 2 doses. Nine patients were evaluable for survival analysis, among whom 6 were available for response assessment at 3 months; best response was stable disease in 3 cases. The median PFS was 2.6 months [95% confidence interval (CI), 0.95–5.75], and the median OS was 10.9 months (95% CI, 8.2–26.6). Conclusions:Intravenous IL13Rα2-targeted CAR T therapy was well tolerated and demonstrated preliminary safety. Further studies are warranted to optimize dosing and preconditioning regimens and identify exploratory biomarkers for efficacy evaluation.

S1. Eligibility criteria S2.Representativeness of study participants S3.Patients’characteristics S4. Release criteria S5. Immunophenotypic composition S6. Individual CAR-T transgene copy number S7. pharmacokinetic parameters in blood S8. Individual patient serum cytokine S9. Median peak time and peak fold change of serum cytokines S10.Individual patient CSF cytokine levels S11. Baseline tumor size and longitudinal radiographic changes

S1. Characteristics of infused YYB-103 S2. MRI of A3-03 S3. Pheripheral blood lymphocyte level S4. Serum testosterone level S5. In vivo expansion profile of YYB-103 in blood and CSF S6. Serum and CSF cytokine profiles S7. Correlation between pheripheral blood CAR-T expansion and longitudinal radiographic changes S8. MRI of A1-03

Purpose: This single-center, open-label, phase I trial evaluated the safety and tolerability of chimeric antigen receptor (CAR) T cells targeting interleukin 13 receptor α2 (IL13Rα2) in patients with malignant gliomas. Patients and Methods: Adults with World Health Organization grade 3 to 4 gliomas, recurrent after standard treatment and expressing IL13Rα2 (confirmed by immunohistochemistry), received a single intravenous infusion of autologous CAR T cells. Primary objectives were to measure the maximum tolerated dose (MTD) and recommended phase II dose. Secondary objectives included assessment of pharmacokinetics, objective response rate, progression-free survival (PFS), and overall survival (OS). Results: Ten patients were sequentially assigned to 3 dosing cohorts (1 × 107, 3 × 107, and 1 × 108 cells/kg). The MTD was not reached, as no dose-limiting toxicities were observed, and all adverse events (AE) were grade ≤3 without irreversible sequelae. The most common treatment-related AE were pyrexia (70%) and elevated transaminase (70%). CAR T-cell levels in blood reached peak concentrations at a median of 7 days (range, 3–14), and the transgene was detected in cerebrospinal fluid from 5 of 6 patients treated at the higher 2 doses. Nine patients were evaluable for survival analysis, among whom 6 were available for response assessment at 3 months; best response was stable disease in 3 cases. The median PFS was 2.6 months [95% confidence interval (CI), 0.95–5.75], and the median OS was 10.9 months (95% CI, 8.2–26.6). Conclusions: Intravenous IL13Rα2-targeted CAR T therapy was well tolerated and demonstrated preliminary safety. Further studies are warranted to optimize dosing and preconditioning regimens and identify exploratory biomarkers for efficacy evaluation.

Kim RH, et al. Brain Tumor Res Treat. 2026 Jul;14(3):137-146. https://doi.org/10.14791/btrt.2026.0029

Parenchymal brain metastasis (BM) and its extended growth into cerebrospinal fluid (CSF) pathways or surgical spillage could result in leptomeningeal metastasis (LM). We defined BM with epipial spread or dural attachment on MRI as BM with CSF space invasion (BM-CSFi), regardless of CSF cytology results, and evaluated its clinical course after BM resection. We retrospectively reviewed 297 patients who underwent craniotomy for BM excluding patients followed for p=0.002), primary small cell lung cancer (HR, 4.92; p=0.026), infratentorial BM location (HR, 2.14; p=0.019), and postoperative cumulative CSF cytology positive rate ≥50% (HR, 7.13; p=0.012) were independent risk factors for LM progression. The mode of resection and postoperative radiotherapy or systemic chemotherapy were not significantly associated with LM progression. BM-CSFi, defined by preoperative MRI findings, may represent a clinically important precursor of LM. Our findings highlight the need for close monitoring of patients with BM-CSFi and the development of management protocols to minimize the risk of LM progression.

Objective: Chordoma, a rare malignant tumor originating from embryonal notochord remnants, exhibits high resistance to conventional treatments, making surgical resection imperative. However, the factors influencing prognosis specifically for cervical spine chordoma have not been clearly identified. We investigate the prognosis of cervical spine chordoma with factors influential in a nationwide multicenter retrospective study.Methods: This study included all patients diagnosed with cervical spine chordoma at 7 tertiary referral centers from January 1998 to March 2023, excluding those with clivus and thoracic spine chordomas extending into the cervical spine. Local recurrence (LR) was identified through follow-up magnetic resonance imaging, either as reappearance in completely resected tumors or regrowth in residual tumors. The study assessed LR and overall survival, analyzing factors influencing LR and death.Results: Forty-five patients with cervical spine chordoma had a mean age of 46.4 years. Over a median follow-up of 52 months, LR and distant metastasis were observed in 21 (46.7%) and 4 patients (8.9%), respectively, and 16 patients (36%) were confirmed dead. The 5-year and 10-year cumulative LR rates were 51.3% and 60%, respectively, while the 5-year and 10-year survival rates were 82% and 53%. Age was the only significant factor affecting mortality (hazard ratio, 1.04; 95% confidence interval, 1.04–1.07; p=0.015). Notably, the degree of resection and adjuvant therapy did not statistically significantly impact local tumor control and mortality.Conclusion: This study, the largest multicenter retrospective analysis of cervical spine chordoma in Korea, identified age as the only factor significantly affecting patient survival.

Objective : To evaluate the usefulness of a cranial implantable chemoport, the H-port, as an alternative to the Ommaya reservoir for intraventricular chemotherapy/cerebrospinal fluid (CSF) access in patients with leptomeningeal metastasis (LM).Methods : One hundred fifty-two consecutive patients with a diagnosis of LM and who underwent H-port installation between 2015 and 2021 were evaluated. Adverse events associated with installation and intraventricular chemotherapy, and the rate of increased intracranial pressure (ICP) control via the port were evaluated for safety and efficacy. These indices were compared with published data of Ommaya (n=89), from our institution.Results : Time-to-install and installation-related complications of intracranial hemorrhage (n=2) and catheter malposition (n=5) were not significantly different between the two groups. Intraventricular chemotherapy-related complications of CSF leakage occurred more frequently in the Ommaya than in the H-port group (13/89 vs. 3/152, respectively, p<0.001). Intracranial hemorrhage during chemotherapy occurred only in the Ommaya group (n=4). The CSF infection rate was not statistically different between groups (14/152 vs. 12/89, respectively). The ICP control rate according to reservoir type revealed a significantly higher ICP control rate with the H-port (40/67), compared with the Ommaya result (12/58, p<0.001). Analyzing the ICP control rate based on the CSF drainage method, continuous extraventricular drainage (implemented only with the H-port), found a significantly higher ICP control rate than with intermittent CSF drainage (33/40 vs. 6/56, respectively, p<0.0001).Conclusion : The H-port for intraventricular chemotherapy in patients with LM was superior for ICP control; it had equal or lower complication rates than the Ommaya reservoir.

Leptomeningeal metastasis (LM) is a common and fatal complication of advanced non-small cell lung cancer (NSCLC) caused by the spread of malignant cells to the leptomeninges and cerebrospinal fluid (CSF). While intra-CSF methotrexate (MTX) chemotherapy can improve prognosis, eventual MTX resistance deters continued chemotherapy. Recent studies have shown that increased miRNA-21 (miR-21) expression in the CSF of patients with LM after intraventricular MTX-chemotherapy is associated with poor overall survival; however, the molecular mechanisms underlying this resistance are poorly understood. Here, we confirm, in 36 patients with NSCLC-LM, that elevated miR-21 expression prior to treatment correlates with poor prognosis. MiR-21 overexpression or sponging results in a corresponding increase or decrease in MTX resistance, demonstrating that cellular miR-21 expression correlates with drug resistance. MiR-21-monitoring sensor and fluorescent extracellular vesicle (EV) staining revealed that EV-mediated delivery of miR-21 could modulate MTX resistance. Moreover, EVs isolated from the CSF of LM patients containing miR-21 could enhance the cell proliferation and MTX resistance of recipient cells. These results indicate that miR-21 can be transferred from cell-to-cell via EVs and potentially modulate MTX sensitivity, suggesting that miR-21 in CSF EVs may be a prognostic and therapeutic target for overcoming MTX resistance in patients with NSCLC-LM.