Duane A. Mitchell
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View article: TMIC-55. Tumor mRNA delivery via microgel-chemokine-mRNA (MCM) complex reprograms microglia and induces glioma regression through CCL4-CCR5 axis
TMIC-55. Tumor mRNA delivery via microgel-chemokine-mRNA (MCM) complex reprograms microglia and induces glioma regression through CCL4-CCR5 axis Open
INTRODUCTION To overcome immunosuppressive tumor microenvironment (TME) in GBM, our group developed ‘onion-like’ mRNA clusters in a microgel–chemokine matrix for enhanced immunogenicity. Instead of lipid particle localization to antigen pr…
View article: TMIC-83. Targeting Lipid Metabolism in GBM: A Systems Biology Strategy to Overcome Treatment-Resistant Persister Cells and Their Myeloid Cell-Mediated Support
TMIC-83. Targeting Lipid Metabolism in GBM: A Systems Biology Strategy to Overcome Treatment-Resistant Persister Cells and Their Myeloid Cell-Mediated Support Open
INTRODUCTION Glioblastoma (GBM) contains metabolically distinct cell lineages: treatment-sensitive cells (TSCs) dependent on glycolysis and treatment-resistant persister cells (TRPCs) reliant on lipid metabolism. Our integrative systems bi…
View article: EXTH-119. Targeting myddosome signaling to improve immunotherapy in melanoma brain metastases
EXTH-119. Targeting myddosome signaling to improve immunotherapy in melanoma brain metastases Open
BACKGROUND Melanoma brain metastases (MBM) develop in up to 60% of patients with metastatic melanoma (MM) and are a major driver of mortality. First-line treatment typically includes immune checkpoint blockade (ICB) with anti-PD-1 and anti…
View article: CTIM-34. PARAPROGRESSION DEFINES A DAMAGE RESPONSE FROM SYSTEMIC MRNA IMMUNOTHERAPY IN MALIGNANT GLIOMA
CTIM-34. PARAPROGRESSION DEFINES A DAMAGE RESPONSE FROM SYSTEMIC MRNA IMMUNOTHERAPY IN MALIGNANT GLIOMA Open
INTRODUCTION Malignant glioma (MG) is a devastating brain tumor with insufficient treatment. Our group has developed a treatment modality for this disease and others, using mRNA wrapped into clusters of lipid particle aggregates (LPAs) for…
View article: Systemic mRNA vaccines elicit rapid immune activation in canine brain tumors
Systemic mRNA vaccines elicit rapid immune activation in canine brain tumors Open
Malignant glioma is considered invariably recalcitrant, thus necessitating development of new therapeutic approaches. Spontaneously arising canine glioma exhibits important molecular and pathological similarities to malignant pediatric gli…
View article: IMMU-62. The Immune Microenvironment and Antigenic Profile of Oligodendrogliomas: Insights for Next-Generation Immunotherapies
IMMU-62. The Immune Microenvironment and Antigenic Profile of Oligodendrogliomas: Insights for Next-Generation Immunotherapies Open
BACKGROUND Efficient immunotherapies for oligodendrogliomas require a detailed understanding of their immunologic landscape and tumor rejection antigens. METHODS To address this, we applied our in-house Open Reading Frame Antigen Network (…
View article: EXTH-109. Overexpressing glucose transporters to enhance CAR-T cell metabolic programming to treat glioblastoma
EXTH-109. Overexpressing glucose transporters to enhance CAR-T cell metabolic programming to treat glioblastoma Open
INTRODUCTION Glioblastoma (GBM) is a brain cancer known for its complex tumor microenvironment and ability to reprogram glucose metabolism and evade host immune responses. CAR-T cell therapy has attracted considerable attention due to its …
View article: EPID-20. The effect of medical comorbidities on survival in GBM: a database study using computed phenotype algorithm for rapid, reliable patient identification
EPID-20. The effect of medical comorbidities on survival in GBM: a database study using computed phenotype algorithm for rapid, reliable patient identification Open
INTRODUCTION Recent clinical trials have demonstrated some improved overall survival of glioblastoma (GBM) compared to historical trials, but this data is often criticized for being homogenous and not easily translated to real-world settin…
View article: OS05.5.A RADIAL GLIAL CELLS AS SOURCE ANTIGEN FOR ADOPTIVE CELLULAR THERAPY IN GLIOBLASTOMA
OS05.5.A RADIAL GLIAL CELLS AS SOURCE ANTIGEN FOR ADOPTIVE CELLULAR THERAPY IN GLIOBLASTOMA Open
BACKGROUND Glioblastoma (GBM) is a highly lethal brain cancer with limited treatment options and poor long-term survival. Adoptive cellular therapy (ACT) has shown promise in targeting GBM, but many ACT strategies rely on patient tumor tis…
View article: Investigating the role of physician communication behaviors on the use of telehealth visits by older Black Americans with chronic conditions
Investigating the role of physician communication behaviors on the use of telehealth visits by older Black Americans with chronic conditions Open
This study found that older Black adults are more likely to use telehealth services when physicians communicate in a manner that is straightforward and includes direct messaging. Additionally, misaligned verbal and nonverbal behaviors may …
View article: Development of a murine laser interstitial thermotherapy system
Development of a murine laser interstitial thermotherapy system Open
OBJECTIVE The objective of this study was to develop a murine system for the delivery of laser interstitial thermotherapy (LITT) with probe-based thermometry as a model for human glioblastoma treatment to investigate thermal diffusion in h…
View article: EXTH-49. DEVELOPMENTAL ANTIGENS CAN TARGET EMBRYONAL PEDIATRIC BRAIN CANCERS IN ADOPTIVE CELLULAR THERAPY
EXTH-49. DEVELOPMENTAL ANTIGENS CAN TARGET EMBRYONAL PEDIATRIC BRAIN CANCERS IN ADOPTIVE CELLULAR THERAPY Open
Mutations in tumor neoantigens have shown promise in immunotherapies for many cancers, yet pediatric brain tumors, which typically have a lower mutational burden, offer fewer opportunities to capitalize on these targeted therapies. Studies…
View article: EXTH-58. BLOCKING IMMUNE CHECKPOINT— LAIR1: DISRUPTING THE LAIR1—FXIII-A—COLLAGEN IMMUNOSUPPRESSIVE CIRCUIT FOR ENHANCED ANTITUMOR THERAPEUTICS
EXTH-58. BLOCKING IMMUNE CHECKPOINT— LAIR1: DISRUPTING THE LAIR1—FXIII-A—COLLAGEN IMMUNOSUPPRESSIVE CIRCUIT FOR ENHANCED ANTITUMOR THERAPEUTICS Open
BACKGROUND Recent evidence indicates that tumor-associated myeloid cells (TAMCs), including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), play a crucial role in glioblastoma (GBM) immunosuppression and p…
View article: CNSC-17. UPREGULATION OF CCL4 AFTER TREATMENT WITH A NOVEL MRNA VACCINE SHIFTS THE PHENOTYPE OF CCR5-EXPRESSING MICROGLIA WITHIN TUMOR MICROENVIRONMENT
CNSC-17. UPREGULATION OF CCL4 AFTER TREATMENT WITH A NOVEL MRNA VACCINE SHIFTS THE PHENOTYPE OF CCR5-EXPRESSING MICROGLIA WITHIN TUMOR MICROENVIRONMENT Open
INTRODUCTION Intra-tumoral immunosuppression is a major cause of treatment failure for patients with glioblastoma (GBM). Our group has developed a proprietary vaccine that combines mRNA encapsulated in lipid nanoparticles with PEG hydrogel…
View article: CTIM-18. HIGH LEVEL OF MUTATIONAL LOAD AND DIVERSITY OF TUMOR INFILTRATING T LYMPHOCYTES ARE FAVORABLE PROGNOSTIC MARKERS FOR CANCER SURVIVAL IN CHILDREN WITH RECURRENT MEDULLOBLASTOMA DURING ADOPTIVE CELLULAR THERAPY
CTIM-18. HIGH LEVEL OF MUTATIONAL LOAD AND DIVERSITY OF TUMOR INFILTRATING T LYMPHOCYTES ARE FAVORABLE PROGNOSTIC MARKERS FOR CANCER SURVIVAL IN CHILDREN WITH RECURRENT MEDULLOBLASTOMA DURING ADOPTIVE CELLULAR THERAPY Open
BACKGROUND Adoptive cellular therapy (ACT) has shown remarkable efficacy in some patients with solid tumors, resulting in durable complete responses. A key mechanism behind this success is the targeting of neoantigens by T cells. There is …
View article: EXTH-48. ADENO-ASSOCIATED VIRUS TARGETING OF THE TUMOR MICROENVIRONMENT TO IMPROVE LYMPHOCYTE RECRUITMENT IN GLIOBLASTOMA
EXTH-48. ADENO-ASSOCIATED VIRUS TARGETING OF THE TUMOR MICROENVIRONMENT TO IMPROVE LYMPHOCYTE RECRUITMENT IN GLIOBLASTOMA Open
BACKGROUND Glioblastoma (GBM) is notoriously devoid of lymphocytes driven in part by a paucity of lymphocyte trafficking factors necessary to prompt their recruitment, infiltration, and activation. We have developed a novel recombinant ade…
View article: CTIM-06. OUTCOME OF PATIENTS WITH RECURRENT MEDULLOBLASTOMA AND EPENDYMOMA TREATED WITH PEMBROLIZUMAB, AN IMMUNE CHECKPOINT INHIBITOR: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY (PBTC045)
CTIM-06. OUTCOME OF PATIENTS WITH RECURRENT MEDULLOBLASTOMA AND EPENDYMOMA TREATED WITH PEMBROLIZUMAB, AN IMMUNE CHECKPOINT INHIBITOR: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY (PBTC045) Open
BACKGROUND Children with recurrent medulloblastoma and ependymoma typically have a dismal prognosis. Immune checkpoint blockade has revolutionized treatment of some resistant cancers. PBTC045 is a safety and preliminary efficacy study of p…
View article: IMMU-31. DAMAGE RESPONSE FROM SYSTEMIC RNA VACCINATION RESTORES HUMORAL IMMUNITY IN GLIOBLASTOMA
IMMU-31. DAMAGE RESPONSE FROM SYSTEMIC RNA VACCINATION RESTORES HUMORAL IMMUNITY IN GLIOBLASTOMA Open
Therapies against glioblastoma (GBM) remain stymied by poor penetration across the blood-brain barrier (BBB) and systemic immunotolerance. These outcomes necessitate development of therapies simultaneously targeted to tumors while engineer…
View article: CTIM-21. FIRST-IN-HUMAN PHASE I CLINICAL TRIAL USING 8R-70CAR T CELLS FOR NEWLY DIAGNOSED ADULT GLIOBLASTOMA
CTIM-21. FIRST-IN-HUMAN PHASE I CLINICAL TRIAL USING 8R-70CAR T CELLS FOR NEWLY DIAGNOSED ADULT GLIOBLASTOMA Open
BACKGROUND To address the challenges of chimeric antigen receptor (CAR) T cell therapy in GBM, we utilized IL-8 release from tumor cells as a ‘GPS homing signal’ to enhance T-cell trafficking with a novel CD70-specific CAR design (8R-70CAR…
View article: CTIM-20. IDENTIFYING CANDIDATE ANTIGEN TARGETS FOR PEDIATRIC BRAIN TUMOR IMMUNOTHERAPIES THROUGH COMPREHENSIVE IMMUNOGENOMIC ANALYSIS
CTIM-20. IDENTIFYING CANDIDATE ANTIGEN TARGETS FOR PEDIATRIC BRAIN TUMOR IMMUNOTHERAPIES THROUGH COMPREHENSIVE IMMUNOGENOMIC ANALYSIS Open
BACKGROUND Identifying tumor rejection antigens continues to be a significant challenge in the development of effective immunotherapies and their application to pediatric brain tumors. METHODS To identify candidate antigen targets for Medu…
View article: TMIC-45. CYTOMEGALOVIRUS PP65 ANTIGEN EXPRESSION FOLLOWING PP65-SPECIFIC DENDRITIC CELL VACCINATION IN MATCHED PRIMARY AND RECURRENT GLIOBLASTOMA SPECIMENS
TMIC-45. CYTOMEGALOVIRUS PP65 ANTIGEN EXPRESSION FOLLOWING PP65-SPECIFIC DENDRITIC CELL VACCINATION IN MATCHED PRIMARY AND RECURRENT GLIOBLASTOMA SPECIMENS Open
BACKGROUND Human cytomegalovirus (HCMV) expression in glioblastoma (GBM) has been corroborated by multiple independent laboratories. HCMV genes have been directly linked to GBM cell proliferation, invasion, and angiogenesis. The HCMV tegum…
View article: IMMU-34. PREDICTION OF TUMOR-ASSOCIATED ANTIGENS USING RADIOGENOMICS
IMMU-34. PREDICTION OF TUMOR-ASSOCIATED ANTIGENS USING RADIOGENOMICS Open
INTRODUCTION Glioblastoma remains a disease with dismal prognosis. Immunotherapy demonstrated promising results against some refractory cancers. However, comparative results have not been accomplished in glioblastoma therapy due to lack of…
View article: TMIC-52. DECODING METABOLIC INTERACTIONS IN GLIOBLASTOMA TUMOR MICROENVIRONMENT THROUGH COMPREHENSIVE SPATIAL TRANSCRIPTOMIC AND PROTEOMIC ANALYSIS
TMIC-52. DECODING METABOLIC INTERACTIONS IN GLIOBLASTOMA TUMOR MICROENVIRONMENT THROUGH COMPREHENSIVE SPATIAL TRANSCRIPTOMIC AND PROTEOMIC ANALYSIS Open
INTRODUCTION Within the GBM microenvironment, distinct micro-niches arise from independent cancer cell lineages with unique metabolic needs, characterized as Fast Cycling Cells (FCCs) and Slow Cycling Cells (SCCs). FCCs preferentially util…
View article: IMMU-21. OVEREXPRESSING CAR T-CELL GLUCOSE TRANSPORTER TO ENHANCE ANTI-TUMOR ACTIVITY IN GLIOBLASTOMA
IMMU-21. OVEREXPRESSING CAR T-CELL GLUCOSE TRANSPORTER TO ENHANCE ANTI-TUMOR ACTIVITY IN GLIOBLASTOMA Open
INTRODUCTION Despite aggressive interventions, Glioblastoma (GBM) remains as a challenge for neuro-oncologists. Standard treatments are often followed by disease recurrence. Adoptive cell therapies have emerged as a viable therapeutic for …
View article: EXTH-09. GENE MODIFICATION OF HEMATOPOIETIC STEM AND PROGENITOR CELLS FOR IMPROVEMENT OF IMMUNOTHERAPIES FOR MALIGNANT GLIOMAS
EXTH-09. GENE MODIFICATION OF HEMATOPOIETIC STEM AND PROGENITOR CELLS FOR IMPROVEMENT OF IMMUNOTHERAPIES FOR MALIGNANT GLIOMAS Open
Patients living with high-grade gliomas have a poor survival prognosis. Furthermore, standard of care treatment for these malignant gliomas has not significantly improved in the past decades. Our laboratory previously demonstrated that the…
View article: IMMU-63. MESSENGER RNA CHALLENGE PREDICTS CANCER IMMUNOGENICITY AND RESPONSE TO CHECKPOINT INHIBITORS
IMMU-63. MESSENGER RNA CHALLENGE PREDICTS CANCER IMMUNOGENICITY AND RESPONSE TO CHECKPOINT INHIBITORS Open
BACKGROUND Checkpoint inhibition has emerged as a promising cancer therapeutic approach. Checkpoint inhibitors (CIs) function by overcoming the adaptive T cell exhaustion induced by solid tumor microenvironment including brain tumors, part…
View article: NVTG-08 PERSONALIZED TREATMENT OF MELANOMA BRAIN METASTASES THROUGH HIGH THROUGHPUT DRUG SCREENING
NVTG-08 PERSONALIZED TREATMENT OF MELANOMA BRAIN METASTASES THROUGH HIGH THROUGHPUT DRUG SCREENING Open
Melanoma is an increasing clinical concern, with an expected increase in incidence over the next 20 years. Compounding this problem, as many as 70% of all metastatic patients will develop brain metastases as a manifestation of their diseas…
View article: Adeno-associated virus delivered CXCL9 sensitizes glioblastoma to anti-PD-1 immune checkpoint blockade
Adeno-associated virus delivered CXCL9 sensitizes glioblastoma to anti-PD-1 immune checkpoint blockade Open
There are numerous mechanisms by which glioblastoma cells evade immunological detection, underscoring the need for strategic combinatorial treatments to achieve appreciable therapeutic effects. However, developing combination therapies is …
View article: TRLS-03. A PHASE 1/2 STUDY ASSESSING SAFETY AND PHARMACOKINETICS OF CEMIPLIMAB IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY SOLID OR CENTRAL-NERVOUS-SYSTEM TUMORS AND SAFETY AND EFFICACY OF CEMIPLIMAB IN COMBINATION WITH RADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA, NEWLY DIAGNOSED HIGH-GRADE GLIOMA, OR RECURRENT HIGH-GRADE GLIOMA
TRLS-03. A PHASE 1/2 STUDY ASSESSING SAFETY AND PHARMACOKINETICS OF CEMIPLIMAB IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY SOLID OR CENTRAL-NERVOUS-SYSTEM TUMORS AND SAFETY AND EFFICACY OF CEMIPLIMAB IN COMBINATION WITH RADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA, NEWLY DIAGNOSED HIGH-GRADE GLIOMA, OR RECURRENT HIGH-GRADE GLIOMA Open
BACKGROUND We investigated, for the first time, combination PD-1 inhibition (cemiplimab) and radiation therapy (RT) followed by cemiplimab monotherapy in children with solid tumors, diffuse intrinsic pontine glioma (DIPG) and high-grade gl…