Glucocorticoids Rapidly Modulate CaV1.2-Mediated Calcium Signals through Kv2.1 Channel Clusters in Hippocampal Neurons

The precise regulation of Ca2+ signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca2+ signals in cultured hippocampal neurons from both female and male rats. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca2+ spikes generated by Kv2.1-organized Ca2+ microdomains. Furthermore, glucocorticoids… Continue reading Glucocorticoids Rapidly Modulate CaV1.2-Mediated Calcium Signals through Kv2.1 Channel Clusters in Hippocampal Neurons

1358 Fatty acid metabolism limits type I interferon responses in irradiated glioblastoma

Background Radiation therapy (RT) induces nucleic acid sensing followed by cancer cell-intrinsic interferon (IFN-I) responses in various cancers. However, combining RT with immunotherapy in glioblastoma has failed to improve patient survival, suggesting robust immunosuppression. Our previous findings showed that RT induces a metabolic shift towards fatty acid synthase (FASN)-mediated lipid synthesis, supporting glioblastoma survival. Since… Continue reading 1358 Fatty acid metabolism limits type I interferon responses in irradiated glioblastoma

1433 Potent tumor antigen expression from dendritic cells through enhanced endosomal escape of mRNA by NanoReady platform, a novel lipid-polymeric nanoparticle for successful cancer immunotherapeutics

Background For a successful mRNA cancer vaccine, delivery of antigen-encoding mRNAs to professional APCs can be achieved by employing delivery vehicles that target lymphoid organ enriched in DCs. After cellular uptake, efficient release of mRNA from the endosome to cytosol is an essential step for antigen protein expression and presentation to T cells. Proper antigen… Continue reading 1433 Potent tumor antigen expression from dendritic cells through enhanced endosomal escape of mRNA by NanoReady platform, a novel lipid-polymeric nanoparticle for successful cancer immunotherapeutics

1427 Precision ImmunomicsTM: identification of hundreds of novel cancer antigens using a sensitive immunopeptidomics-led platform

Background The discovery and characterization of tumor-specific antigens are critical for advancing cancer immunotherapies, including next-generation cancer vaccines. A mass spectrometry (MS)-based approach, such as immunopeptidomics, is widely recognized as the optimal method to identify expressed and presented antigens. However, despite its high selectivity, immunopeptidomics could benefit from improved sensitivity, as evidenced by the low… Continue reading 1427 Precision ImmunomicsTM: identification of hundreds of novel cancer antigens using a sensitive immunopeptidomics-led platform

1442 Comparison of human immune cell repertoire in five CD34 HSC engrafted NSG/SGM3 mouse strains

Background Increasingly complex molecules developed to treat cancer; i.e. immuno-oncology bispecifics, antibody-drug-conjugates, cell therapy, various cell checkpoint inhibitors, demands mouse model systems able to handle complex biological hypotheses. Evolution of the immune-humanized mouse has allowed scientists to directly test human tumors and molecules in these mice without the need for surrogate molecules. First generations of… Continue reading 1442 Comparison of human immune cell repertoire in five CD34 HSC engrafted NSG/SGM3 mouse strains

1425 BSI-118, a novel anti-B7H7 antibody antagonizing B7H7-KIR3DL3 signaling pathway without affecting B7H7-TMIGD2 stimulatory signaling pathway

Background Being the youngest known molecule of the B7 family, B7H7 is a newly emerging immune checkpoint with unique immunomodulatory characteristics. B7H7 exerts co-stimulatory activity upon interaction with transmembrane and immunoglobulin domain containing 2 (TMIGD2), a member of CD28 family that mainly expressed on resting or naïve T cells. B7H7 exerts coinhibitory activity through binding… Continue reading 1425 BSI-118, a novel anti-B7H7 antibody antagonizing B7H7-KIR3DL3 signaling pathway without affecting B7H7-TMIGD2 stimulatory signaling pathway

1423 BSI-120, a fully human anti-MICA/B antibody with enhanced Fc receptor function, prevents MICA/B shedding and reinforces anti-tumor immunity

Background Major histocompatibility complex class I chain-related protein A (MICA) and B (MICB) are highly polymorphic transmembrane proteins with low levels of expression at steady state, but are up-regulated on a wide variety of human tumors. MICA/B act as activating ligands for natural killer group 2 member D (NKG2D) which mediates tumor surveillance, enabling elimination… Continue reading 1423 BSI-120, a fully human anti-MICA/B antibody with enhanced Fc receptor function, prevents MICA/B shedding and reinforces anti-tumor immunity

1424 BSI-115, a novel anti-V{gamma}9V{delta}2 agonist monoclonal antibody, promotes V{gamma}9V{delta}2 T cell activity against tumor cells

Background V9V2, also known as T cell antigen receptor, is composed of a chain including V9 (TRGV9) and C (TRGC) and a chain including V2 (TRDV2) and C (TRDC). V9V2 is expressed on V9V2 T cells which represent 1–5% population of all circulating T cells (~95% of circulating T cells1), but it can increase to… Continue reading 1424 BSI-115, a novel anti-V{gamma}9V{delta}2 agonist monoclonal antibody, promotes V{gamma}9V{delta}2 T cell activity against tumor cells

1435 Therapeutic mRNA cancer vaccine for GBM reaches complete response in a preclinical model

Background Glioblastoma (GBM) is a fatal cancer that has limited response to chemotherapy and radiotherapy. Immunotherapy for GBM has been challenging due to low frequency of neoantigens and immunosuppressive tumor microenvironment. Here we report the efficacy of a novel EGFRvIII mRNA vaccine formulated in next generation lipid nanoparticles (LNP). EGFRvIII is a cancer-driver mutation detected… Continue reading 1435 Therapeutic mRNA cancer vaccine for GBM reaches complete response in a preclinical model

975 Tumor Treating Fields (TTFields) elicit macrophage pro-inflammatory phenotype skewing

Background Tumor Treating Fields (TTFields) are electric fields that disrupt cellular processes critical for cancer cell viability. In preclinical models, TTFields have been shown to induce cancer immunogenic cell death and elicit a systemic anti-cancer immune response. In a phase 3 study, TTFields co-application with an immune checkpoint inhibitor (ICI) demonstrated benefit in patients with… Continue reading 975 Tumor Treating Fields (TTFields) elicit macrophage pro-inflammatory phenotype skewing