Volumetric Nanodroplet-Enhanced Ultrasound Surgery Combined with Immune Checkpoint Inhibition as a Cancer Therapy Platform.

Immune checkpoint inhibitors hold promise, yet their efficacy in solid tumors is limited by the complex tumor microenvironment and the lack of immune cell infiltration. This study aims to enhance immunotherapy by combining anti PD-1 checkpoint inhibition therapy with nanodroplet-mediated histotripsy. The proposed method involves systemic injection of nanodroplets, which accumulate within tumors.

The Clinical Significance of Circulating Lymphocytes Morphology in Diffuse Large B-Cell Lymphoma As Determined by a Novel, Highly Sensitive Microscopy.

Chimeric Antigen Receptor T-cell (CAR T) therapy has become the preferable treatment in relapsed/refractory diffuse large B-cell lymphomas (DLBCL) patients. Detection of CAR Ts in peripheral blood smear (PBS) is challenging due to insufficient data regarding their morphology and low sensitivity. The morphological evolution of CAR Ts along their production process, and in patients, was established by Full-Field Morphology (FFM), a novel digital microscopy approach that provides highly sensitive PBS analysis.

Nanoscale CAR Organization at the Immune Synapse Correlates with CAR-T Effector Functions.

T cells expressing chimeric antigen receptors (CARs) are at the forefront of clinical treatment of cancers. Still, the nanoscale organization of CARs at the interface of CAR-Ts with target cells, which is essential for TCR-mediated T cell activation, remains poorly understood. Here, we studied the nanoscale organization of CARs targeting CD138 proteoglycans in such fixed and live interfaces, generated optimally for single-molecule localization microscopy.

Comparing Intraperitoneal and Intravenous Personalized ErbB2CAR-T for the Treatment of Epithelial Ovarian Cancer.

High-grade serous ovarian carcinoma (HGSOC) is the most common type of epithelial ovarian cancer. The majority of cases are diagnosed at advanced stages, when intraperitoneal (IP) spread has already occurred. Despite significant surgical and chemotherapeutic advances in HGSOC treatment over the past decades, survival rates with HGSOC have only modestly improved.

Extracellular Vesicles Derived from Chimeric Antigen Receptor-T Cells: A Potential Therapy for Cancer.

Chimeric antigen receptor (CAR)-T cells are genetically engineered T cells, directed against a tumor-associated antigen. Extracellular vesicles (EVs) derived from CAR-T cells (CAR-T EVs) may preserve CAR-T activity and overcome one of the major obstacles responsible for CAR-T cell failure in patients with solid tumors. This study aimed to compare CAR-T EVs with their parental cells and explore their cell penetration and cytotoxic activity.

Shaping Functional Avidity of CAR T Cells: Affinity, Avidity, and Antigen Density That Regulate Response.

Chimeric antigen receptors (CARs) are immunoreceptors that redirect T cells to selectively kill tumor cells. Given their clinical successes in hematologic malignancies, there is a strong aspiration to advance this immunotherapy for solid cancers; hence, molecular CAR design and careful target choice are crucial for their function. To evaluate the functional significance of the biophysical properties of CAR binding (i.

Treatment of Multiple Myeloma Using Chimeric Antigen Receptor T Cells with Dual Specificity.

Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable successes in fighting B-cell leukemias/lymphomas. Promising response rates are reported in patients treated with B-cell maturation antigen (BCMA) CAR T cells for multiple myeloma. However, responses appear to be nondurable, highlighting the need to expand the repertoire of multiple myeloma-specific targets for immunotherapy and to generate new CAR T cells.

MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma.

Immunotherapy using mucin 1 (MUC1) linked to oxidised mannan (MFP) was investigated in an aggressive MUC1+ metastatic tumour, DA3-MUC1 because, unlike many MUC1+ tumour models, DA3-MUC1 is not spontaneously rejected in mice making it an alternative model for immunotherapy studies. Further, DA3-MUC1 cells are resistant to lysis by anti-MUC1 cytotoxic T cells (CTLs). The inability of DA3-MUC1 tumours to be rejected in naïve mice as well as vaccination to MUC1 was attributed to a deficiency of expression of MHC class I molecules on the tumour cell surface.

Cell surface-associated anti-MUC1-derived signal peptide antibodies: implications for cancer diagnostics and therapy.

The MUC1 tumor associated antigen is highly expressed on a range of tumors. Its broad distribution on primary tumors and metastases renders it an attractive target for immunotherapy. After synthesis MUC1 is cleaved, yielding a large soluble extracellular alpha subunit containing the tandem repeats array (TRA) domain specifically bound, via non-covalent interaction, to a smaller beta subunit containing the transmembrane and cytoplasmic domains.

Epizootic hemorrhagic disease virus induces and benefits from cell stress, autophagy, and apoptosis.

The mode and timing of virally induced cell death hold the potential of regulating viral yield, viral transmission, and the severity of virally induced disease. Orbiviruses such as the epizootic hemorrhagic disease virus (EHDV) are nonenveloped and cytolytic. To date, the death of cells infected with EHDV, the signal transduction pathways involved in this process, and the consequence of their inhibition have yet to be characterized.

Characterization of novel multiantigenic vaccine candidates with pan-HLA coverage against Mycobacterium tuberculosis.

The low protection by the bacillus Calmette-Guérin (BCG) vaccine and existence of drug-resistant strains require better anti-Mycobacterium tuberculosis vaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived from M. tuberculosis antigens.

Autoantibodies against the signal peptide domain of MUC1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis.

Naturally generated autoantibodies to tumor-associated antigens such as MUC1 can assist in cancer diagnosis and prognosis. While previous studies have concentrated on the tandem repeat array domain of MUC1, here we focused on MUC1's signal peptide domain. We used ELISA assays with MUC1-specific epitopes and antibodies to quantify soluble MUC1 antigen and anti-MUC1 autoantibodies against the tandem repeat array and signal peptide domains in 15 naïve donors and 27 multiple myeloma cancer patients.

ImMucin: a novel therapeutic vaccine with promiscuous MHC binding for the treatment of MUC1-expressing tumors.

An optimal cancer vaccine should be able to induce highly potent, long-lasting, tumor-specific responses in the majority of the cancer patient population. One approach for achieving this is to use synthetic peptide vaccines derived from widely expressed tumor-associated antigens, that promiscuously bind multiple MHC class I and class II alleles. MUC1-SP-L (ImMucin, VXL100) is a 21mer peptide encoding the complete signal peptide domain of MUC1, a tumor-associated antigen expressed by over 90% of solid and non-solid tumors.

Negative regulation of the endocytic adaptor disabled-2 (Dab2) in mitosis.

Mitotic cells undergo extensive changes in shape and size through the altered regulation and function of their membrane trafficking machinery. Disabled 2 (Dab2), a multidomain cargo-specific endocytic adaptor and a mediator of signal transduction, is a potential integrator of trafficking and signaling. Dab2 binds effectors of signaling and trafficking that localize to different intracellular compartments.

ERK and PI3K regulate different aspects of the epithelial to mesenchymal transition of mammary tumor cells induced by truncated MUC1.

Epithelial to mesenchymal transition (EMT) integrates changes to cell morphology and signaling pathways resulting from modifications to the cell's transcriptional response. Different combinations of stimuli ignite this process in the contexts of development or tumor progression. The human MUC1 gene encodes multiple alternatively spliced forms of a polymorphic oncoprotein that is aberrantly expressed in epithelial malignancies.