B7-H3 CAR-T / St. Jude Children's Research Hospital - LARVOL DELTA

CSF immune profiling after intracranial B7-H3-CAR T cell therapy for pediatric brain tumors: Insights from a Phase I clinical study (ASGCT 2026) - "Organized by the Modified Immune Effector Cell Committee."

CAR T-Cell Therapy • Clinical • P1 data • Brain Cancer • Oncology • Pediatrics • Solid Tumor • CD276

Tumor inflammation-associated neurotoxicity in children with diffuse intrinsic pontine glioma receiving B7-H3-targeting CAR T cells on BrainChild-03. (PubMed, Neurooncol Pract) - P1 | "This study retrospectively applies TIAN criteria to patients with DIPG/pontine DMG treated with intraventricular B7-H3 CAR T cells in the BrainChild-03 (BC-03) trial (NCT04185038)...TIAN was common within this cohort but mostly low-grade and transient. Refining its classification and understanding its clinical impact will aid safety assessments and trial comparisons for CNS-directed CAR T therapies."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Pain • Pediatrics • Solid Tumor • Ventriculomegaly • CD276

Evaluating Efficacy of B7-H3-CAR T Cells Administered at the End of Upfront Map Chemotherapy in Patients With Newly Diagnosed High-Risk Osteosarcoma (clinicaltrials.gov) - P2 | N=41 | Not yet recruiting | Sponsor: St. Jude Children's Research Hospital

New P2 trial • Lung Cancer • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial. (PubMed, Nat Med) - P1 | "Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial. ClinicalTrials.gov registration: NCT04185038 ."

Journal • P1 data • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Fatigue • Glioma • Hematological Disorders • Oncology • Pain • Pediatrics • Solid Tumor

CSF Immune Profiling after Intracranial B7-H3-CAR T Cell Therapy for Pediatric Brain Tumors: Insights from a Phase I Clinical Study (SNO 2025) - No abstract available

CAR T-Cell Therapy • Clinical • P1 data • Brain Cancer • Oncology • Pediatrics • Solid Tumor • CD276

Tumor inflammation-associated neurotoxicities for patients treated with intracranial B7-H3-CAR T cells on a phase I clinical trial (SNO 2025) - P1 | "TIAN-2 occurred in 10/21 (48%) patients and 23/87 (26%) infusions. Overall, it is important to harmonize reporting of neurological AEs in CNS immunotherapy trials, with the goal to better capture, understand and improve supportive care for patients receiving CNS-directed CAR T-cell therapies."

CAR T-Cell Therapy • Clinical • P1 data • Brain Cancer • CNS Disorders • CNS Tumor • Epilepsy • Neuralgia • Oncology • Otorhinolaryngology • Vertigo • CD276

Dual CD123 and B7-H3 CAR T Cells Potentiate Immune Responses and Remodel the Tumor Microenvironment in Pediatric Gliomas (SNO 2025) - "In vivo, CD123 CAR T-cells were administered intratumorally as monotherapy or in combination with B7-H3 CAR T-cells. Targeted depletion of CD123+ TAMs enhances B7-H3 CAR T-cell efficacy by mitigating immunosuppressive signaling while preserving beneficial myeloid support. This dual-targeting strategy offers a mechanistically guided approach to overcoming TME-driven resistance in DIPG and other pHGG."

Biomarker • CAR T-Cell Therapy • Clinical • Tumor microenvironment • Brain Cancer • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • CD123 • CD276 • IL3RA

Improving intravenous B7-H3 CAR T cell treatment for DMG using MRgFUS (SNO 2025) - "This body of work supports the continued investigation of combinatorial CAR T therapy and MRgFUS for DMG. Future studies will determine if combination therapy produces a survival advantage over monotherapies and is translatable to a fully immunocompetent model of DMG."

CAR T-Cell Therapy • Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor • CD276

Increased capacity for expansion, not persistence, improves preclinical B7-H3 targeted CAR T cell therapy against aggressive Group 3 medulloblastomas (SNO 2025) - P1 | "In this work, we sought to determine whether improving the capacity of B7-H3 CAR-T cells to 1) persist or 2) expand against G3MB would improve anti-tumor efficacy in patient derived xenograft (PDX) models...We show that Regnase-1 KO indeed improves the anti-tumor efficacy of patient CAR-T cells in vivo. This is highly significant as the fitness of patient T cells is often drastically impaired from exposure to previous therapies and support translation of Regnase-1 deleted CAR-T cells into early phase clinical testing for PBTs."

CAR T-Cell Therapy • Preclinical • Brain Cancer • Medulloblastoma • Solid Tumor • CD276 • DNMT3A • TET2

Cell-free DNA analysis of CSF samples enables assessment of treatment response and tracking of CAR T-cells post-locoregional delivery in pediatric brain tumor patients (SNO 2025) - P1 | "Here, we leveraged 127 CSF liquid biopsies collected from 9 pediatric CNS tumor patients undergoing B7H3-CAR T-cell therapy (NCT05835687) for simultaneous assessment of circulating tumor DNA (ctDNA) and CAR T-cell cfDNA...Transient subclonal alterations emerging in response to treatment were identified in a subset of patients. In summary, CSF liquid biopsies capture ctDNA and CAR T-cell cfDNA dynamics, providing a sensitive platform for detecting treatment response, disclosing mechanisms of resistance, and monitoring CAR T-cell persistence and expansion."

CAR T-Cell Therapy • Cell-free DNA • Clinical • Brain Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • CD276

Deciphering how DNA methylation programs in diffuse midline glioma influence CAR T cell efficacy in fully immune-competent murine models (SNO 2025) - "Transcriptomics analyses are ongoing to elucidate the immediate interaction between the DMG TIME and B7-H3.CAR T cells during the treatment. Together, our findings reveal that epigenetic programs modulate the DMG TIME and potentially influence B7-H3.CAR T therapeutic efficacy."

CAR T-Cell Therapy • Epigenetic controller • Preclinical • Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor • CD276 • DNMT3A

Optimizing CAR T-Cell therapy in group 3 medulloblastoma through tumor microenvironment modulation and blood-brain barrier disruption (SNO 2025) - "In parallel, low-intensity focused ultrasound (LIFU) provides a noninvasive method to transiently disrupt the BBB, potentially enhancing both immunomodulatory effects and CAR T-cell infiltration.Objective: To improve the efficacy of B7-H3-directed CAR T-cell therapy in G3MB by optimizing CAR design, reprogramming the TME using POx-encapsulated Resiquimod (POx-R), and enhancing tumor accessibility with LIFU. We engineered B7-H3 CARs with CD28, 4-1BB, or dual costimulatory domains and tested their efficacy in vitro and in vivo... This multimodal strategy of integrating CAR engineering, myeloid reprogramming, and BBB modulation offers a promising path to overcome the key barriers limiting CAR T-cell therapy in G3MB."

Biomarker • CAR T-Cell Therapy • IO biomarker • Tumor microenvironment • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • CD276

CAR T-cells targeted to B7-H3 are effective against ependymomas but show limited response in the immune competent setting (SNO 2025) - "We generated second-generation mouse and human B7-H3-CAR T-cells and examined their anti-EPN functionality in vitro and in vivo...Together, our study establishes clinically relevant models to study CAR T-cell therapy resistance in EPN, and preliminary mechanistic insight into CAR T-cell persistence and modulation through CCL2 signaling. Additionally, our work is the first to evaluate CAR T-cell efficacy against EPNs in the syngeneic setting."

CAR T-Cell Therapy • Ependymoma • Oncology • Solid Tumor • CCL2

Dual CD123 and B7-H3 CAR T Cells Potentiate Immune Responses and Remodel the Tumor Microenvironment in Pediatric Gliomas (SNO 2025) - "In vivo, CD123 CAR T-cells were administered intratumorally as monotherapy or in combination with B7-H3 CAR T-cells. Targeted depletion of CD123+ TAMs enhances B7-H3 CAR T-cell efficacy by mitigating immunosuppressive signaling while preserving beneficial myeloid support. This dual-targeting strategy offers a mechanistically guided approach to overcoming TME-driven resistance in DIPG and other pHGG."

Biomarker • CAR T-Cell Therapy • Clinical • Tumor microenvironment • Brain Cancer • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • CD123 • CD276 • IL3RA

Cell-free DNA analysis of CSF samples enables assessment of treatment response and tracking of CAR T-cells post-locoregional delivery in pediatric brain tumor patients (SNO 2025) - P1 | "Here, we leveraged 127 CSF liquid biopsies collected from 9 pediatric CNS tumor patients undergoing B7H3-CAR T-cell therapy (NCT05835687) for simultaneous assessment of circulating tumor DNA (ctDNA) and CAR T-cell cfDNA...Transient subclonal alterations emerging in response to treatment were identified in a subset of patients. In summary, CSF liquid biopsies capture ctDNA and CAR T-cell cfDNA dynamics, providing a sensitive platform for detecting treatment response, disclosing mechanisms of resistance, and monitoring CAR T-cell persistence and expansion."

CAR T-Cell Therapy • Cell-free DNA • Clinical • Brain Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • CD276

Improving intravenous B7-H3 CAR T cell treatment for DMG using MRgFUS (SNO 2025) - "This body of work supports the continued investigation of combinatorial CAR T therapy and MRgFUS for DMG. Future studies will determine if combination therapy produces a survival advantage over monotherapies and is translatable to a fully immunocompetent model of DMG."

CAR T-Cell Therapy • Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor • CD276

Identification of clinically actionable drugs that enhance CAR-T cell expansion and cytotoxicity against DMG (SNO 2025) - "To conduct a targeted screen of selected compounds, we first labeled DMG tumor cells with Renilla luciferase and B7-H3 CAR T cells with firefly luciferase...Staurosporine and DMSO were used as positive and negative controls for cell death, respectively, while Dasatinib served as a T cell-specific negative control...Notably, our screen recovered previously reported hits such as Lenalidomide and Birinipant, supporting the validity of our approach. We are currently evaluating the top three compounds that enhance both CAR T cell expansion and tumor cell killing in vitro and in vivo. Collectively, we have optimized a method to perform screens involving multiple variables which will support the ongoing efforts to investigate combinatorial treatment strategies for CAR T cells against DMGs."

CAR T-Cell Therapy • Clinical • Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor • CD276

Increased capacity for expansion, not persistence, improves preclinical B7-H3 targeted CAR T cell therapy against aggressive Group 3 medulloblastomas (SNO 2025) - P1 | "In this work, we sought to determine whether improving the capacity of B7-H3 CAR-T cells to 1) persist or 2) expand against G3MB would improve anti-tumor efficacy in patient derived xenograft (PDX) models...We show that Regnase-1 KO indeed improves the anti-tumor efficacy of patient CAR-T cells in vivo. This is highly significant as the fitness of patient T cells is often drastically impaired from exposure to previous therapies and support translation of Regnase-1 deleted CAR-T cells into early phase clinical testing for PBTs."

CAR T-Cell Therapy • Preclinical • Brain Cancer • Medulloblastoma • Solid Tumor • CD276 • DNMT3A • TET2

Tumor inflammation-associated neurotoxicities for patients treated with intracranial B7-H3-CAR T cells on a phase I clinical trial (SNO 2025) - P1 | "TIAN-2 occurred in 10/21 (48%) patients and 23/87 (26%) infusions. Overall, it is important to harmonize reporting of neurological AEs in CNS immunotherapy trials, with the goal to better capture, understand and improve supportive care for patients receiving CNS-directed CAR T-cell therapies."

CAR T-Cell Therapy • Clinical • P1 data • Brain Cancer • CNS Disorders • CNS Tumor • Epilepsy • Neuralgia • Oncology • Otorhinolaryngology • Vertigo • CD276

Locoregional B7-H3 CAR-T cells for relapsed/refractory CNS tumors: preliminary clinical experience of the Loc3CAR trial (SNO 2025) - P1 | "Two patients met off-study criteria due to suspected disease progression but received additional infusions on single-patient protocols with subsequent clinical benefit. Our findings demonstrate that treatment with DL1 and DL2 have an acceptable safety profile so far, and show signals of activity, warranting ongoing investigation into this therapeutic approach."

CAR T-Cell Therapy • Clinical • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Ependymoma • Glioma • Medulloblastoma • Oncology • Otorhinolaryngology • Solid Tumor • Vertigo • CD276

Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Ewing Sarcoma • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

MACROPHAGE INHIBITION ENHANCES PERIPHERAL CAR T CELL EXPANSION AND TUMOR CONTROL IN A PATIENT-DERIVED HUMANIZED MODEL OF AUTOLOGOUS CAR T CELL EFFICACY IN PEDIATRIC OSTEOSARCOMA (OS) (CTOS 2025) - "NSG-SGM3 mice were humanized by injection of patient HSCs after busulfan ablation and autologous CAR T cell efficacy was assessed against orthotopic LM7 OS tumors. Macrophage inhibition with the small molecule BLZ945 was assessed in combination with B7-H3 CAR T cells in Hu-pHSC and nonhumanized mice. CD34+ HSCs engrafted into NSG-SGM3 mice with mean peripheral human engraftment of 10% after 8 weeks... Hu-pHSC mice developed from OS patient bone marrow products allow investigation of the effect of the patient's inhibitory immune environment on CAR T cell efficacy. In this model, CAR T cells had limited antitumor activity, as in early phase clinical trials, unless macrophages were depleted. This model improves on standard xenograft models and has the potential to serve as a reliable avatar for modeling immunotherapeutics for OS."

CAR T-Cell Therapy • Clinical • IO biomarker • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD276 • CD34 • IFNG • IL10 • IL4 • IL6

CSF Immune Profiling after Intracranial B7-H3-CAR T Cell Therapy for Pediatric Brain Tumors: Insights from a Phase I Clinical Study (WFNOS 2025) - No abstract available

CAR T-Cell Therapy • Clinical • P1 data • Brain Cancer • Pediatrics • Solid Tumor • CD276

Increased capacity for expansion, not persistence, improves preclinical B7-H3 targeted CAR T cell therapy against aggressive Group 3 medulloblastomas (WFNOS 2025) - P1 | "In this work, we sought to determine whether improving the capacity of B7-H3 CAR-T cells to 1) persist or 2) expand against G3MB would improve anti-tumor efficacy in patient derived xenograft (PDX) models...We show that Regnase-1 KO indeed improves the anti-tumor efficacy of patient CAR-T cells in vivo. This is highly significant as the fitness of patient T cells is often drastically impaired from exposure to previous therapies and support translation of Regnase-1 deleted CAR-T cells into early phase clinical testing for PBTs."

CAR T-Cell Therapy • Preclinical • Brain Cancer • Medulloblastoma • Solid Tumor • CD276 • DNMT3A • TET2

Dual CD123 and B7-H3 CAR T Cells Potentiate Immune Responses and Remodel the Tumor Microenvironment in Pediatric Gliomas (WFNOS 2025) - "In vivo, CD123 CAR T-cells were administered intratumorally as monotherapy or in combination with B7-H3 CAR T-cells. Targeted depletion of CD123+ TAMs enhances B7-H3 CAR T-cell efficacy by mitigating immunosuppressive signaling while preserving beneficial myeloid support. This dual-targeting strategy offers a mechanistically guided approach to overcoming TME-driven resistance in DIPG and other pHGG."

Biomarker • CAR T-Cell Therapy • Clinical • Tumor microenvironment • Brain Cancer • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • CD123 • CD276 • IL3RA