GD2-CART / Stanford University - LARVOL DELTA

Unravelling temporal dynamics of GD2-CAR T cell therapy in H3K27M-mutant diffuse midline glioma through comprehensive single-cell and multi-omic profiling (AACR 2025) - P1 | "By contextualizing single-cell data within multi-omic frameworks and clinical outcomes, this study advances our understanding of the GD2-CAR T cell therapy, the tumor microenvironment, and biomarkers of response and resistance. These findings provide critical insights for optimizing CAR T cell therapies in CNS malignancies and inform the development of next-generation immunotherapies."

CAR T-Cell Therapy • IO biomarker • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor • TGFB1

Myeloid Populations Modulate GD2 CAR T cell Activity in Diffuse Midline Glioma Patients (SITC-SSC 2025) - No abstract available

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

Intravenous and intracranial GD2-CAR T cells for H3K27M+ diffuse midline gliomas. (PubMed, Nature) - P1 | "Nine patients demonstrated neurological benefit, as measured by a protocol-directed clinical improvement score. Sequential IV, followed by ICV GD2-CART, induced tumour regressions and neurological improvements in patients with DIPG and those with sDMG."

CAR T-Cell Therapy • Journal • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Myeloid populations modulate GD2 CAR T cell activity in diffuse midline glioma (SNO 2024) - P1 | "Together, these data display the power of in-depth correlative analyses to identify distinct immune populations that drive durability of response. Key findings from these data will allow for optimization of CAR-T therapies for H3K27M+ DMG patients, providing hope to shift the paradigm of this fatal disease."

CAR T-Cell Therapy • Clinical • IO biomarker • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Rejuvenated iPSC-derived GD2-directed CART cells harbor robust cytotoxicity against small cell lung cancer. (PubMed, Cancer Res Commun) - "Dual blockade of TIGIT and programmed death-1 (PD-1) increased the cytotoxicity of GD2-CARTs to some extent, suggesting that low TIGIT and PD-1 expression of GD2-CARrejTs is a major factor required for robust cytotoxicity against SCLC. Not only for robust cytotoxicity but also for availability as "off-the-shelf" T cell therapy, iPSC-derived GD2-CARrejTs are a promising novel treatment for SCLC."

CAR T-Cell Therapy • IO biomarker • Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • TIGIT

Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy. (PubMed, Cancer Cell) - P1 | "Longitudinal analysis of post-treatment samples identified increased CXCR3 classical monocytes in all groups as CAR-T numbers waned. Together, our data uncover mediators of CAR-T biology and correlates of expansion that could be utilized to advance immunotherapies for solid tumor patients."

CAR T-Cell Therapy • Journal • CNS Tumor • Neuroblastoma • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor • CXCR3

GD2-CAR T Clinical Trial for Diffuse Intrinsic Pontine Gliomas (DIPGs) and Spinal Diffuse Midline Gliomas (DMGs) (SNO 2023) - No abstract available

Clinical • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Combining FLASH Radiotherapy with GD2-CAR T cell immunotherapy in diffuse intrinsic pontine glioma (SNO 2023) - "Additionally, we have found that GD2 expression on DIPG tumor cells remains unchanged upon treatment with FLASH-RT. Therefore, we can utilize FLASH-RT to target GD2 CART while sparing normal tissue and minimizing neurotoxicity, allowing for a promising avenue of combination treatment for this devastating pediatric cancer."

CAR T-Cell Therapy • IO biomarker • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG) & Spinal Diffuse Midline Glioma(DMG) (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Crystal Mackall, MD | Trial completion date: Jul 2042 ➔ Jul 2043

CAR T-Cell Therapy • Trial completion date • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG) & Spinal Diffuse Midline Glioma(DMG) (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Crystal Mackall, MD | Trial primary completion date: Jul 2027 ➔ Jul 2028

CAR T-Cell Therapy • Trial primary completion date • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing. (PubMed, Mol Cancer) - "Our work provides a novel platform to perform guided CAR insertion into primary human T-cells using nanoplasmid DNA and holds the potential to increase access to CAR-T cell therapies."

CAR T-Cell Therapy • Journal • Multiple Myeloma • Oncology • Solid Tumor

Immune determinants of CAR-T expansion in solid tumor patients receiving GD2 CAR-T cell therapy (AACR 2023) - P1 | "CXCR3 has been extensively studied on T cells, but its function on myeloid populations is yet to be fully explored. These results are the first to demonstrate that the peripheral immune environment prior to CAR-T administration may effectively predict and modulate CAR-T expansion in patients."

CAR T-Cell Therapy • Clinical • IO biomarker • CNS Tumor • Hematological Malignancies • Leukemia • Lymphoma • Neuroblastoma • Neuroendocrine Tumor • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CXCR3

Immune signatures of GD2 CAR T cell activity in H3K27M+ diffuse midline glioma patients (AACR 2023) - P1 | "H3K27M-mutated DIPG/DMG patients demonstrate continued clinical response with serial ICV GD2 CAR-T infusions, with heterogeneity in the durability of response across patients. In-depth correlative analyses profile distinct immune populations and demonstrate population shifts depending on route of administration and over the course of treatment. Key findings from these data will allow for iterative improvement in CAR-T therapies for H3K27M+ DIPG/DMG patients, providing hope to shift the paradigm of this fatal disease."

CAR T-Cell Therapy • Clinical • IO biomarker • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor • CCL2 • CXCL9 • IFNG • IL6

Defining T cell exhaustion and memory correlates of GD2 CAR T cell expansion in pediatric patients with solid tumor malignancies (SITC 2022) - P1 | "We identified phenotypic, transcriptomic, and epigenetic T cell signatures correlating with CAR-T expansion. These data suggest key mechanisms of underlying T cell biology that may contribute to CAR-T activity in pediatric solid tumors."

CAR T-Cell Therapy • Clinical • IO biomarker • CNS Tumor • Neuroblastoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD19 • CD22 • CD8

GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG) & Spinal Diffuse Midline Glioma(DMG) (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Crystal Mackall, MD | Trial completion date: Dec 2023 ➔ Jul 2042 | Trial primary completion date: Dec 2023 ➔ Jul 2027

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor