Background An immunoactive complex consisting of a polyethyleneimine derivative (2E’), cytotoxic drug, and nucleotide is developed to stimulate innate immune cells in solid tumors. Each component has unique roles: 2E’ induces the maturation of antigen-presenting cells (APC) and promotes the release of immunostimulatory cytokines. 2E’ can also induce immunogenic cell death (ICD) in tumor cells.… Continue reading 713 IMmunoActive compleX (IMAX) for immunotherapy of solid tumors
Tag: Nucleic Acid Biochemistry
712 Modeling response to alkylating chemotherapy in a syngeneic model of MMR-deficient glioma
Background Glioblastoma (GBM) carries a dismal prognosis with a median survival under 15 months. Temozolomide (TMZ) is the standard frontline chemotherapeutic treatment in glioblastoma patients and works by depositing a methyl group to purine bases of DNA (O6-guanine; N7-guanine and N3-adenine. The O6-methylguanine (O6-MeG) lesion is directly repaired by O6-Methylguanine Methyltransferase (MGMT). In tumor cells… Continue reading 712 Modeling response to alkylating chemotherapy in a syngeneic model of MMR-deficient glioma
714 Anti-CD40 and epigenetic modifier inhibitors to augment treatment of high-risk neuroblastoma
Background Neuroblastoma is the most common pediatric extracranial solid tumor with ~50% of patients having high-risk disease (HR-NBL). HR-NBL patients undergo multimodal therapy that includes anti-GD2 immunotherapy. While some patients receiving this regimen respond, ~50% develop refractory or relapsed disease. Considered a ‘cold’ tumor, most HR-NBLs have infiltration of suppressive immune cells [including type-2 tumor… Continue reading 714 Anti-CD40 and epigenetic modifier inhibitors to augment treatment of high-risk neuroblastoma
748 Localized STING agonist delivery via liposome-MDP hydrogel composites plus systemic {alpha}-PD-1 and {alpha}-CTLA-4 improves immunotherapy responses
Background Head and Neck Squamous Cell Carcinoma (HNSCC), the sixth most common cancer worldwide, is associated with high-risk subtypes of human papillomavirus (HPV), tobacco, and alcohol over-consumption. Standard of care treatments include surgery, radiation or chemoradiation. Five-year survival rates for patients with locoregionally advanced HNSCC have not significantly improved in decades and remain at approximately… Continue reading 748 Localized STING agonist delivery via liposome-MDP hydrogel composites plus systemic {alpha}-PD-1 and {alpha}-CTLA-4 improves immunotherapy responses
575 Epigenetic modulation by KDM6B in myeloid cells regulates glioblastoma immune checkpoint therapy outcomes
Background Glioblastoma (GBM), a disease with a grim overall prognosis, exhibits inherent resistance to immune checkpoint therapy (ICT). GBM tumors notably contain immune-suppressive myeloid cell subsets, which contribute to this resistance. The potential to enhance ICT response by targeting specific epigenetic pathways to reprogram these immune-suppressive myeloid cells into an immune-stimulatory phenotype remains largely unexplored.… Continue reading 575 Epigenetic modulation by KDM6B in myeloid cells regulates glioblastoma immune checkpoint therapy outcomes
553 Depletion of effector regulatory T cells drives major response to induction dual immune checkpoint blockade (ICB) in patients with oropharyngeal carcinoma (OPC)
Background Pathological response to neoadjuvant ICB is established as a biomarker of long-term disease control in several solid tumors.1 To determine tumor microenvironment (TME) features associated with pathological response, we performed single-cell profiling on matched baseline and on-treatment tumor biopsies from patients with newly diagnosed HPV-positive OPC enrolled in a phase 2 trial of a… Continue reading 553 Depletion of effector regulatory T cells drives major response to induction dual immune checkpoint blockade (ICB) in patients with oropharyngeal carcinoma (OPC)
530 Antigen-dependent differentiation and expansion of tumor-infiltrating CD8+ T cell clonotypes occurs in the spleen in response to immune checkpoint blockade
Background Immune checkpoint blockade (ICB) provides durable clinical and survival benefits for a fraction of cancer patients.1–3 ICB blocks interactions between inhibitory receptors expressed by exhausted CD8+ T cells and their ligands expressed by tumor cells or antigen-presenting cells, enhancing the functionality and clonal expansion of CD8+ T cells, thereby improving the overall anti-tumor immune… Continue reading 530 Antigen-dependent differentiation and expansion of tumor-infiltrating CD8+ T cell clonotypes occurs in the spleen in response to immune checkpoint blockade
525 Adenosine uptake through equilibrative nucleoside transporter-1 suppresses antitumor immunity by pyrimidine starvation
Background Immunosuppression by adenosine is an important cancer immune checkpoint. Extracellular adenosine can signal through specific receptors or be transported across the cell membrane through nucleoside transporters. While adenosine receptors are known to regulate tumor immunity, the impact of adenosine transporters remains unknown. In this study, we investigated the effect on tumor immunity of equilibrative… Continue reading 525 Adenosine uptake through equilibrative nucleoside transporter-1 suppresses antitumor immunity by pyrimidine starvation
427 Cancer neutrophil encyclopedia: a deep dive into antigen-presenting warriors
Background Neutrophils, the most efficient defenders against pathogens, are essential for tumor microenvironment balance and homeostasis.1–3 However, given their plasticity and short half-life which made them too fragile to be profiled, it poses complex challenges regarding how neutrophils are imprinted and adapt specific fates across cancers.4–7 Methods Here we designed a one-two-punch sorting strategy, generated… Continue reading 427 Cancer neutrophil encyclopedia: a deep dive into antigen-presenting warriors
341 Onboard, tethered cytokines boost potency and maintain selectivity of a Tmod NOT gate
Background Constructs that express cytokines in immune cells are a powerful potential add-on to cell therapies. Onboard, membrane-tethered cytokines can mitigate some of the shortcomings of exogenous cytokines, including systemic toxicity, short half-life, and poor tissue penetration. However, in the case of engineered logic gates, designed to improve tumor-specific killing by integrating signals from multiple… Continue reading 341 Onboard, tethered cytokines boost potency and maintain selectivity of a Tmod NOT gate