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Logun, M.

Publications and source records attributed to Logun, M..

2 recordsLinked to original sources

CAR-T cells locally delivered in porcine decellularized matrix hydrogels enhance survival in post-resection glioblastoma

Patients diagnosed with glioblastoma (GBM) receive a devastating prognosis of less than 15 months, and recurrence of GBM is most often local, suggesting that regional therapies would serve both immediate and long-term needs of patients. Here, we investigate a biomaterials-based approach for local delivery of chimeric antigen receptor (CAR) T cells using a murine model of partial GBM resection that mimics patient recurrence. We demonstrate that hydrogel delivery of CAR T cells directly into the intracranial resection cavity can stably implant cellular immunotherapies against CNS solid tumors, and significantly prolongs survival in recurrent GBM-bearing mice compared to those receiving resection alone. One Sentence SummaryDuring resection surgeries for brain tumors, delivering cell therapy at time of surgery could improve outcomes for patients.

cancer biology↗

Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy

Patient-derived tumor organoids have been leveraged for disease modeling and preclinical studies, but rarely applied in real-time to aid with interpretation of patient treatment responses in clinics. We recently demonstrated early efficacy signals in a first-in-human, phase 1 study of dual-targeting chimeric antigen receptor T cells (EGFR-IL13R2 CAR-T cells) in patients with recurrent glioblastoma. Here we analyzed six sets of patient-derived glioblastoma organoids (GBOs) treated concurrently with the same autologous CAR-T cell products as patients in our phase 1 study. We found that CAR-T cell treatment led to target antigen reduction and cytolysis of tumor cells in GBOs, the degree of which correlated with CAR-T cell engraftment detected in patients cerebrospinal fluid (CSF). Furthermore, cytokine release patterns in GBOs mirrored patient CSF samples over time. Our findings highlight a unique trial design and GBOs as a valuable platform for real-time assessment of CAR-T cell bioactivity and insights into immunotherapy efficacy.

cancer biology↗