Justin Low
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View article: EXTH-35. ATM/DNA-PK Inhibitor XRD-0394 Enhances Radiation-Induced Pro-Inflammatory Responses in Glioma Models
EXTH-35. ATM/DNA-PK Inhibitor XRD-0394 Enhances Radiation-Induced Pro-Inflammatory Responses in Glioma Models Open
High-grade gliomas, including glioblastomas (GBMs) and diffuse midline gliomas (DMGs) are aggressive brain tumors that inevitably recur despite treatment with standard therapies, including radiation therapy. Tumor cell persistence may be p…
View article: INNV-39. Response to next interventions after treatment with off-label ivosidenib in patients with mutant IDH low grade glioma
INNV-39. Response to next interventions after treatment with off-label ivosidenib in patients with mutant IDH low grade glioma Open
The introduction of mutant IDH inhibitors (mIDHi) has transformed the treatment landscape for patients with low-grade gliomas (LGG). However, optimal strategies for tumor control following progression on mIDHi therapy remain uncertain. We …
View article: CTIM-30. INVESTIGATION OF THE COMBINATION OF D2C7-IT WITH AN FC-ENGINEERED ANTI-HUMANCD40 MONOCLONAL ANTIBODY (2141-V11) WHEN ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOLLOWED BY CERVICAL PERILYMPHATIC INJECTIONS (CPLIS) OF 2141-V11 COMPARED TO D2C7-IT CED MONOTHERAPY IN PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM)
CTIM-30. INVESTIGATION OF THE COMBINATION OF D2C7-IT WITH AN FC-ENGINEERED ANTI-HUMANCD40 MONOCLONAL ANTIBODY (2141-V11) WHEN ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOLLOWED BY CERVICAL PERILYMPHATIC INJECTIONS (CPLIS) OF 2141-V11 COMPARED TO D2C7-IT CED MONOTHERAPY IN PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM) Open
BACKGROUND When administered via CED in glioma models, D2C7-IT, an antibody toxin conjugate, combined with an anti-mouseCD40 generates robust antitumor immunity by killing tumor cells, activating microglia, reversing glioma-associated micr…
View article: TIP-25. Randomized phase 2 clinical trial of repeated intratumoral and cervical perilymphatic injections (CPLIs) of lerapolturev vs. lomustine in recurrent glioblastoma (rGBM): safety lead-in results
TIP-25. Randomized phase 2 clinical trial of repeated intratumoral and cervical perilymphatic injections (CPLIs) of lerapolturev vs. lomustine in recurrent glioblastoma (rGBM): safety lead-in results Open
BACKGROUND Lerapolturev is a modified, non-pathogenic version of the Sabin™ type 1 poliovirus vaccine that infects myeloid compartments within the tumor microenvironment to generate antitumor immunity by stimulating tumor antigen cross-pre…
View article: TIP-27. An assessment of the Tumor Monorail Device (TMD) for repeated sampling as part of a trial evaluating the combination of D2C7-IT and an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery (CED) and cervical perilymphatic injections (CPLIs) of 2141-V11 in recurrent glioblastoma (rGBM) patients
TIP-27. An assessment of the Tumor Monorail Device (TMD) for repeated sampling as part of a trial evaluating the combination of D2C7-IT and an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery (CED) and cervical perilymphatic injections (CPLIs) of 2141-V11 in recurrent glioblastoma (rGBM) patients Open
BACKGROUND The TMD is a surgically implanted catheter system that remains in place after tumor resection. The TMD is not used to deliver therapy but serves as a platform to monitor changes in the tumor environment post-treatment, potential…
View article: BIOM-79. TARGETING FGFR ALTERATIONS IN GLIOMAS: A SINGLE-INSTITUTION CASE SERIES
BIOM-79. TARGETING FGFR ALTERATIONS IN GLIOMAS: A SINGLE-INSTITUTION CASE SERIES Open
BACKGROUND Fibroblast growth factor receptor (FGFR) alterations are a potentially actionable target in various cancers, including glioblastoma (GBM). FGFR inhibitors have shown variable efficacy in GBM to date. We present a single-institut…
View article: Clinical Trial of Feasibility for Mindfulness Intervention for Patients with Newly Diagnosed High Grade Glioma
Clinical Trial of Feasibility for Mindfulness Intervention for Patients with Newly Diagnosed High Grade Glioma Open
Purpose. With a bleak prognosis for malignant glioma, maintaining quality of life (QoL) and decreasing distress are essential in patient clinical care. Mindfulness meditation is a mind-body therapy that is being investigated as a non-pharm…
View article: A real-time imaging approach to quantify dendritic cell internalization for immunogenicity risk assessment of biotherapeutics
A real-time imaging approach to quantify dendritic cell internalization for immunogenicity risk assessment of biotherapeutics Open
The presence of treatment-emergent anti-drug antibodies (ADAs) can pose challenges during biotherapeutic development by compromising drug safety and efficacy. Early assessment of immunogenicity risk is essential to mitigate these risks. De…
View article: Epigenetic modulation elicits an NK cell-mediated immune response in urothelial carcinoma
Epigenetic modulation elicits an NK cell-mediated immune response in urothelial carcinoma Open
Urothelial carcinoma (UC), the second most prevalent cancer of the urothelial system, has demonstrated a well-developed ability to evade natural killer (NK) cell-mediated killing via various pathways, highlighting the need for innovative t…
View article: Beyond DNA damage response: Immunomodulatory attributes of CHEK2 in solid tumors
Beyond DNA damage response: Immunomodulatory attributes of CHEK2 in solid tumors Open
The CHEK2 gene serves a canonical role in the DNA damage response (DDR) pathway encoding the regulatory kinase CHK2 in the homologous recombination (HR) repair of double-strand breaks (DSB). Although CHEK2 is traditionally co…
View article: Taking the STING out of radiotherapy: STING checkpoints mediate radiation resistance
Taking the STING out of radiotherapy: STING checkpoints mediate radiation resistance Open
The cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway is a critical driver of type I interferon (IFN-I) and antitumor CD8+ T cell responses after radiotherapy (RT). In this issue of the JCI, two reports describe m…
View article: Understanding and therapeutically exploiting cGAS/STING signaling in glioblastoma
Understanding and therapeutically exploiting cGAS/STING signaling in glioblastoma Open
Since the discovery that cGAS/STING recognizes endogenous DNA released from dying cancer cells and induces type I interferon and antitumor T cell responses, efforts to understand and therapeutically target the STING pathway in cancer have …
View article: Data from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence
Data from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence Open
Purpose:Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant …
View article: Supplementary Data F1 from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence
Supplementary Data F1 from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence Open
Supplementary Figures
View article: Data from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence
Data from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence Open
Purpose:Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant …
View article: Supplementary Data T1 from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence
Supplementary Data T1 from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence Open
Supplementary Tables
View article: Supplementary Data T1 from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence
Supplementary Data T1 from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence Open
Supplementary Tables
View article: Supplementary Data F1 from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence
Supplementary Data F1 from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence Open
Supplementary Figures
View article: EPCO-50. THE TRANSCRIPTIONAL LANDSCAPE OF KEY INNATE DNA SENSORS WITHIN PRIMARY BRAIN TUMORS
EPCO-50. THE TRANSCRIPTIONAL LANDSCAPE OF KEY INNATE DNA SENSORS WITHIN PRIMARY BRAIN TUMORS Open
Primary brain tumors are notoriously resistant to immunotherapy. The efficacy of these treatments potentially requires normal expression of DNA innate sensors within both the immune and tumor compartments. Recently, we found that STING1, i…
View article: EPCO-43. STING EPIGENETIC SILENCING IN GBM: IMPLICATIONS FOR INFLAMING THE IMMUNE MICROENVIRONMENT AND DESIGNING COMBINATION THERAPIES
EPCO-43. STING EPIGENETIC SILENCING IN GBM: IMPLICATIONS FOR INFLAMING THE IMMUNE MICROENVIRONMENT AND DESIGNING COMBINATION THERAPIES Open
Primary brain tumors including glioblastoma (GBM) are notoriously resistant to immunotherapy due in part to disrupted innate immunity. The stimulator of interferon genes (STING) pathway is a key component of innate immunity and senses path…
View article: CTIM-09. PHASE 1/1B TRIAL OF FC-ENGINEERED ANTI-CD40 AGONIST MONOCLONAL ANTIBODY (2141-V11) INFUSED WITH D2C7-IT IN ENHANCING DISEASE BY CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (RMG)
CTIM-09. PHASE 1/1B TRIAL OF FC-ENGINEERED ANTI-CD40 AGONIST MONOCLONAL ANTIBODY (2141-V11) INFUSED WITH D2C7-IT IN ENHANCING DISEASE BY CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (RMG) Open
BACKGROUND D2C7-IT is a dual-specific immunotoxin. Recombinant antibody fragments bind the wild-type epidermal growth factor receptor (EGFRwt) and its mutant EGFR variant III (EGFRvIII), triggering internalization and intracellular deliver…
View article: Use, access, and initial outcomes of off-label ivosidenib in patients with IDH1 mutant glioma
Use, access, and initial outcomes of off-label ivosidenib in patients with IDH1 mutant glioma Open
Background Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes gliomagenesis and is implicated in epileptogenesis. Ivosidenib (IVO)…
View article: Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence
Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence Open
Purpose: Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant…
View article: Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy
Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy Open
View article: TMIC-10. IDENTIFICATION, VALIDATION AND BIOLOGICAL CHARACTERIZATION OF NOVEL GLIOBLASTOMA TUMOUR MICROENVIRONMENT SUBTYPES: IMPLICATIONS FOR PRECISION IMMUNOTHERAPY
TMIC-10. IDENTIFICATION, VALIDATION AND BIOLOGICAL CHARACTERIZATION OF NOVEL GLIOBLASTOMA TUMOUR MICROENVIRONMENT SUBTYPES: IMPLICATIONS FOR PRECISION IMMUNOTHERAPY Open
New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles, have failed to direct treatment strategies. We hypothesized that interrogation of the…
View article: BIOM-43. THE GENOMIC, TRANSCRIPTOMIC, AND EPIGENOMIC LANDSCAPE OF ISOCITRATE DEHYDROGENASE WILD TYPE GLIOBLASTOMA ACROSS THE AGE CONTINUUM
BIOM-43. THE GENOMIC, TRANSCRIPTOMIC, AND EPIGENOMIC LANDSCAPE OF ISOCITRATE DEHYDROGENASE WILD TYPE GLIOBLASTOMA ACROSS THE AGE CONTINUUM Open
BACKGROUND Older age is a poor prognostic factor for glioblastoma (GBM) patients. We tested whether the intrinsic molecular landscape of the tumor may contribute to this poor prognosis. METHODS In accordance with the 2021 WHO classificatio…
View article: CTIM-23. DOSE ESCALATION TRIAL OF FC-ENGINEERED ANTI-CD40 MONOCLONAL ANTIBODY (2141-V11) ADMINISTERED INTRATUMORALLY WITH D2C7-IT VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMAS (RMGS)
CTIM-23. DOSE ESCALATION TRIAL OF FC-ENGINEERED ANTI-CD40 MONOCLONAL ANTIBODY (2141-V11) ADMINISTERED INTRATUMORALLY WITH D2C7-IT VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMAS (RMGS) Open
BACKGROUND D2C7-IT, a novel immunotoxin-based cytotoxic therapy, targets epidermal growth factor receptor (EGFR) and mutant EGFR variant III. In preclinical studies, D2C7-IT kills tumor cells and prolongs survival, but is unable to generat…
View article: cGAS-STING pathway targeted therapies and their applications in the treatment of high-grade glioma
cGAS-STING pathway targeted therapies and their applications in the treatment of high-grade glioma Open
Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide …
View article: BSCI-20 STING EPIGENETIC SILENCING IN GLIOMAS CAN BE RESCUED BY METHYLTRANSFERASE INHIBITION: IMPLICATIONS FOR NOVEL THERAPEUTIC APPROACHES
BSCI-20 STING EPIGENETIC SILENCING IN GLIOMAS CAN BE RESCUED BY METHYLTRANSFERASE INHIBITION: IMPLICATIONS FOR NOVEL THERAPEUTIC APPROACHES Open
The stimulator of interferon genes (STING) is a key component of the innate immune response to pathogenic cytosolic DNA, resulting in IRF3- and NFκB-dependent transcription of type I interferons (IFN) and pro-inflammatory cytokines. STING …
View article: Patterns of care in adult histone mutant gliomas: Results of an international survey
Patterns of care in adult histone mutant gliomas: Results of an international survey Open
Background Histone mutant gliomas (HMG) with histone H3 K27 and G34 mutations are recognized as biologically discrete entities with distinct anatomical locations, younger age at presentation (in comparison to the most common high-grade gli…