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

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

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 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Initiation date: Jun 2026 ➔ Sep 2026

Trial initiation date • Lung Cancer • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma. (PubMed, Cell Rep Med) - "In immune-competent models, Reg-1 KO also endowed murine B7-H3-CAR T cells with the ability to create a proinflammatory landscape characterized by an influx of interferon gamma (IFN-γ)-producing endogenous T cells and natural killer (NK) cells and a reduction of inhibitory myeloid cells, including M2-like macrophages. Thus, deleting Reg-1 has cell- and non-cell-autonomous benefits, nominating Reg-1 KO B7-H3-CAR T cells as a promising cell product for early-phase clinical testing in patients with solid tumors."

Biomarker • Journal • Gene Therapies • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD276 • IFNG

Potent anti-tumor preclinical efficacy of B7-H3 CAR-T cells in H3G34-mutant, Diffuse Hemispheric Glioma. (PubMed, Neuro Oncol) - "This study provides preclinical evidence supporting B7-H3 CAR T cell therapy as a highly effective immunotherapeutic strategy for DHG. Our findings support B7-H3 as a compelling immunotherapeutic target for DHG, laying the groundwork for clinical translation."

IO biomarker • Journal • Preclinical • Brain Cancer • CNS Tumor • Glioma • Hematological Malignancies • High Grade Glioma • Leukemia • Oncology • Pediatrics • Solid Tumor • CD276

Intracerebroventricular B7-H3-targeting CAR T cells for non-pontine DMG and recurrent/refractory pediatric CNS tumors: a phase 1 trial. (PubMed, Neuro Oncol) - P1 | "Repeated ICV B7-H3 CAR T cell dosing is feasible and tolerable across a spectrum of pediatric CNS tumors, supporting continued investigation in future trials."

Journal • P1 data • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Embryonal Tumor • Ependymoma • Glioma • High Grade Glioma • Medulloblastoma • Oncology • Pain • Pediatrics • Pineoblastoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • CD276

Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Recruiting ➔ Active, not recruiting | N=48 ➔ 29 | Trial primary completion date: Mar 2028 ➔ Jun 2026

Enrollment change • Enrollment closed • Trial primary completion date • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Ependymoma • Glioblastoma • Glioma • High Grade Glioma • Medulloblastoma • Oncology • Pediatrics • Rhabdoid Tumor • Sarcoma • Solid Tumor • CD276

CAR T cells generated from pediatric brain tumor patients have limited in vivo antitumor efficacy (ISPNO 2026) - P1 | "Herein, we investigated the functionality of B7-H3 CAR T cells generated from 9 pediatric brain tumor patients on our ongoing Loc3CAR clinical trial (NCT05835687)...These results demonstrate that CAR T cells derived from pediatric brain tumor patients have inherently limited fitness, leading to poor tumor control in vivo and possibly contributing to the lack of clinical responses. Future work will focus on identifying targetable mechanisms to improve the fitness of brain tumor patient CAR T cells to enhance therapeutic efficacy."

CAR T-Cell Therapy • Preclinical • Brain Cancer • Hematological Malignancies • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • CD276 • CD4

Characterizing and optimizing EphA2-targeted CAR T-cells for Group 3 medulloblastoma therapy (ISPNO 2026) - "To contextualize our results, we compared EphA2-CAR T-cells with 4H5 scFv and CD28ζ signaling to clinically relevant B7-H3-CAR T-cells with MGA271 scFv and CD28ζ signaling. We show that genetic deletion of DNMT3A or Regnase-1, or expression of a constitutive active IL-18 receptor significantly enhanced in vivo efficacy, while MyD88.CD40 co-stimulation or expression of a constitutively active IL-2 receptor did not. Together, our results support continued clinical development of EphA2-targeted CAR T-cells for G3MB."

CAR T-Cell Therapy • IO biomarker • Brain Cancer • Medulloblastoma • Solid Tumor • CD276 • CD40 • DNMT3A • EPHA2 • IL18 • IL2 • MYD88

Neuroimaging beyond TIAN: novel neuroimaging patterns in pediatric patients undergoing intracranial B7-H3-CAR T cell therapy (ISPNO 2026) - "Together, these findings demonstrate intracranial B7-H3-CAR T cells can lead to transient, basilar inflammatory meningitis, associated with new cranial nerve palsies. Systematic evaluation of the relationship between neuroimaging findings and clinical symptoms across clinical trials is critical to better characterize these associations and potentially inform risk assessment for future pediatric patients receiving intracranial CAR T cell therapy.References:1. Vitanza, Nicholas A., et al."

CAR T-Cell Therapy • Clinical • Brain Cancer • CNS Disorders • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Infectious Disease • Pediatrics • Solid Tumor • Ventriculomegaly • CD276

Tailored gene-editing to improve B7-H3 CAR T-cell therapy for group 3 medulloblastoma (ISPNO 2026) - P1 | "We show that Regnase-1 KO indeed improves the anti-tumor efficacy of patient-derived B7-H3-CAR T-cells in vivo, nominating Regnase-1 KO B7-H3 CAR-T cells as a future CAR T-cell product for clinical testing for pediatric brain tumors. Beyond the translational relevance of our work, our study highlights that the benefit of deleting negative regulators in T cells is CAR-dependent, highlighting the need to delineate underlying mechanisms going forward."

CAR T-Cell Therapy • Brain Cancer • Medulloblastoma • Solid Tumor • CD276 • CD4 • DNMT3A • TET2

Targeting TAM and microglial states to potentiate B7‑H3 CAR T‑cell therapy in Group 3 Medulloblastoma (ISPNO 2026) - "Optimizing CAR design and reprogramming myeloid populations improve CAR T‑cell efficacy against G3MB. This strategy addresses key barriers in pediatric brain tumor immunotherapy and supports the development of TME‑informed CAR T‑cell approaches for high‑risk medulloblastoma."

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

Monitoring of B7-H3-CAR T cell trafficking via [89Zr]PET Imaging (SNMMI 2026) - "[89Zr]oxine facilitates robust production of [89Zr] labeled B7-H3-CAR T cells that may enable longitudinal tracking of CAR T cells in vivo. Initial PET/MRI studies with [89Zr] labeled B7-H3-CAR T cells showed pronounced accumulation of [89Zr] in liver and spleen and limited signal at the tumor site, consistent with organ uptake in control mice. These findings highlight complexities of [89Zr]oxine labeling for PET-based tracking of CAR T cell biodistribution in vivo and support the need for additional studies to determine biological effects of radiolabeling on CAR T cells and clarify factors that influence [89Zr] accumulation in tumors compared to normal tissues."

CAR T-Cell Therapy • Ewing Sarcoma • Osteosarcoma • Sarcoma • Solid Tumor • CD276 • IFNG

Monitoring of B7-H3-CAR T cell trafficking via [89Zr]PET Imaging (SNMMI 2026) - "[89Zr]oxine facilitates robust production of [89Zr] labeled B7-H3-CAR T cells that may enable longitudinal tracking of CAR T cells in vivo. Initial PET/MRI studies with [89Zr] labeled B7-H3-CAR T cells showed pronounced accumulation of [89Zr] in liver and spleen and limited signal at the tumor site, consistent with organ uptake in control mice. These findings highlight complexities of [89Zr]oxine labeling for PET-based tracking of CAR T cell biodistribution in vivo and support the need for additional studies to determine biological effects of radiolabeling on CAR T cells and clarify factors that influence [89Zr] accumulation in tumors compared to normal tissues."

CAR T-Cell Therapy • Ewing Sarcoma • Osteosarcoma • Sarcoma • Solid Tumor • CD276 • IFNG

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

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 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

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 | Initiation date: Feb 2026 ➔ Jun 2026

Trial initiation date • Lung Cancer • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

Single-cell profiling of CSF immune dynamics following intracranial B7-H3 CAR T cell therapy for pediatric brain tumors (IMMUNOLOGY 2026) - "Our study shows that single-cell profiling of CSF immune cell components is feasible and revealed dynamic immune remodeling following intracranial B7-H3 CAR T therapy. Repeated infusions promoted CAR+ T cell accumulation but also expanded potentially suppressive Tregs and signaling-active myeloid subsets, highlighting targets for future therapeutic refinement."

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

TIRTL-sequencing to interrogate the clonal repertoire of CARpos and CARneg TILs post CAR T-cell therapy for pediatric solid tumors (IMMUNOLOGY 2026) - P1 | "We are investigating B7-H3-CAR T cells for pediatric patients on two early phase clinical trials... TILs can be expanded from small tumor fragments post-CAR T cell infusion. TIRTL-seq is a scalable platform for αβ TCR-seq for limited cells recovered from cultured TILs. TIRTL-seq analyses suggest TIL clonal expansion and segment usage patterns vary significantly, whereas some show strong clonal expansion and others display high diversity."

CAR T-Cell Therapy • Clinical • Brain Cancer • Cognitive Disorders • Ependymoma • Oncology • Pediatrics • Sarcoma • Solid Tumor • Synovial Sarcoma • CD276 • CD8 • PTPRC

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR) (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: St. Jude Children's Research Hospital | N=32 ➔ 48 | Trial completion date: Mar 2027 ➔ Mar 2028 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Enrollment change • Trial completion date • Trial primary completion date • Adrenal Cortex Carcinoma • Brain Cancer • Ewing Sarcoma • Genito-urinary Cancer • Germ Cell Tumors • Hepatoblastoma • Melanoma • Nephrology • Neuroblastoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • CD276

RASA2 deletion rescues immune synapse dysfunction, enhancing CAR T cell efficacy against DMGs. (PubMed, J Immunother Cancer) - "Our study highlights the importance of understanding tumor-specific factors that limit CAR T-cell response and using this information to design superior next-generation CAR T-cells. Specifically, we identify cytoskeleton remodeling and T cell motility as therapeutically actionable targets for future engineering approaches."

Journal • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioblastoma • Glioma • 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

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