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Principal Investigator: Catalina Lee Chang
Organization: NORTHWESTERN UNIVERSITY AT CHICAGO
Fiscal Year: 2024
Award: $347,701
Funding agency: National Cancer Institute
PROJECT SUMMARY/ABSTRACT
Immunotherapy has revolutionized the treatment of many tumors. However, most GBM patients
have not, so far, benefited from immunotherapeutic treatment. With the goal of exploring ways to
boost anti-GBM immunity, we've developed a B-cell-based vaccine (BVax) that consists of 4-1BBL+
B cells activated with CD40 agonism, BAFF and IFNγ stimulation. BVax migrate to key secondary
lymphoid organs and are proficient at antigen cross-presentation, which promotes both the
survival and functionality of CD8+ T cells. A combination of radiation, BVax, and PD-L1 blockade
conferred tumor eradication in 80% of treated tumor-bearing animals. This research proposal
aims to understand the immune mechanisms underlying this protection and prevention of tumor
growth. We will focus on two processes: generation of CD8+ T-cell memory formation (Aim 1) and
Ab production (Aim 2). We hypothesize that both effector functions elicit protective anti-GBM
immunity.
We have been successful at generating GBM patient-derived BVax that activated autologous CD8+
T cells, which shows a strong ability to kill autologous glioma cells. This demonstrates that BVax
can be produced from patient's peripheral blood. We now aim to further characterize and optimize
BVax treatment protocol to inform future clinical application of this therapeutic approach (Aim 3).
Overall, our study provides a novel alternative to current immunotherapeutic approaches that can
be readily translated to the clinic.
Terms: <APC Vaccine><Ab response><Animals><Antibodies><Antibody Formation><Antibody Production><Antigen Presentation><Antigens><Authorization><Authorization documentation><Autologous><B blood cells><B cell><B cell differentiation><B cell receptor><B cells><B lymphocyte differentiation><B-Cell Activation><B-Cell Antigen Receptor><B-Cell Development><B-Cells><B-Lymphocytes><B-cell><Bp50><Brain><Brain Nervous System><CD40><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD86><CD86 gene><CD8B><CD8B1><CD8B1 gene><CDW40><Cell Body><Cell Mediated Immunology><Cell Therapy><Cell-Mediated Immunity><Cells><Cellular Immunity><Characteristics><Circulation><Class I Genes><Clinic><Clinical Evaluation><Clinical Testing><Cross Presentation><Data><Dendritic Cells><Early-Stage Clinical Trials><Encephalon><Ensure><Evaluation><Future><Generations><Glial Cell Tumors><Glial Neoplasm><Glial Tumor><Glioblastoma><Glioma><Goals><Grade IV Astrocytic Neoplasm><Grade IV Astrocytic Tumor><Grade IV Astrocytoma><Humoral Immunities><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><IL-15><IL15><IL15 Protein><IgG1><Immune><Immune Interferon><Immune mediated therapy><Immunes><Immunity><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologically Directed Therapy><Immunologics><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Immunotherapeutic agent><Immunotherapy><Infiltration><Interferon Gamma><Interferon Type II><Interleukin-15><Interleukin-15 Precursor><Investigational New Drug Application><Knowledge><LYT3><Lytotoxicity><MGC9013><MGC9721><MHC Class I><MHC Class I Genes><Mediating><Memory><Metabolic><Mice><Mice Mammals><Murine><Mus><Myelogenous><Myeloid><Neuroglial Neoplasm><Neuroglial Tumor><PD-L1 blockade><PDL1 blockade><Patients><Permission><Phase 1 Clinical Trials><Phase I Clinical Trials><Prevention><Process><Production><Radiation><Research><Research Proposals><Specificity><T cell infiltration><T memory cell><T-Cell Activation><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><TNFRSF5><TNFRSF5 gene><Testing><Therapeutic><Therapeutic antibodies><Toxicology><Translating><Treatment Protocols><Treatment Regimen><Treatment Schedule><Tumor Antigens><Tumor Immunity><Tumor Necrosis Factor Receptor Superfamily Member 5 Gene><Tumor-Associated Antigen><Vaccine Production><Vaccines><Veiled Cells><Work><aPD-L1><aPDL1><activate T cells><activated B cells><anti programmed cell death ligand 1><anti programmed cell death protein ligand 1><anti-PD-(L)1><anti-PD-L1><anti-PD-L1 blockade><anti-PDL-1><anti-PDL1><anti-tumor immunity><antiPD-L1><antiPDL1><antibody biosynthesis><antibody-based immunity><antigen-presenting cell vaccine><antitumor immunity><cancer antigens><cancer immune therapeutics><cancer immunity><cancer immunotherapeutics><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular therapeutic><cellular therapy><check point blockade><checkpoint blockade><clinical applicability><clinical application><clinical test><cost><cytokine><cytotoxic><cytotoxicity><design><designing><efficacy study><experiment><experimental research><experimental study><experiments><glial-derived tumor><glioblastoma multiforme><immune check point blockade><immune checkpoint blockade><immune drugs><immune suppression><immune suppressive activity><immune suppressive function><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapeutics><immune-based therapies><immune-based treatments><immuno therapy><immunogen><immunoglobulin biosynthesis><immunologic therapeutics><immunosuppressive activity><immunosuppressive function><immunosuppressive response><immunotherapeutics><immunotherapy agent><in vivo><lFN-Gamma><memory T lymphocyte><migration><neuroglia neoplasm><neuroglia tumor><novel><p50><peripheral blood><phase 1 designs><phase I designs><phase I protocol><pre-clinical efficacy><pre-clinical study><pre-clinical toxicity><preclinical efficacy><preclinical study><preclinical toxicity><prevent><preventing><produce vaccines><research clinical testing><secondary lymph organ><secondary lymphatic organ><secondary lymphoid organ><spongioblastoma multiforme><thymus derived lymphocyte><tumor><tumor eradication><tumor growth><tumor-specific antigen><vaccine for immunotherapy><vaccine immunotherapy><vaccine-based immunotherapy><αPD-L1><αPDL1>