67 research outputs found

    FUNCTIONALIZED LATERAL SURFACE COATED LASERS FOR CHEM-BIO DETECTION

    Get PDF
    We present a class of compact, monolithic, photonic sensors consisting of multiple section edge emitting lasers with functionalized lateral surface coatings for low level detection of chemical or biological agents. Specifically, we discuss 8 {micro}m x 250 {micro}m Pd-coated H{sub 2} sensors and configurations to reduce the minimum detection limit from 138ppm for passive sensors to 1ppm for active sensors. Compared with conventional optical H{sub 2} sensors that use fiber gratings, surface plasmon resonances, or surface reflectance, our sensors offer the advantages of smaller size, wider dynamic range, monolithic integration of laser source and detector, and 2-D scalability to arrays of sensors that are functionalized to detect different agents

    Tumor-responsive, multifunctional CAR-NK cells cooperate with impaired autophagy to infiltrate and target glioblastoma

    Get PDF
    Tumor antigen heterogeneity, a severely immunosuppressive tumor microenvironment (TME) and lymphopenia resulting in inadequate immune intratumoral trafficking have rendered glioblastoma (GBM) highly resistant to therapy. As a result, GBM immunotherapies have failed to demonstrate sustained clinical improvements in patient overall survival (OS). To overcome these obstacles, here we describe a novel, sophisticated combinatorial platform for GBM: the first multifunctional immunotherapy based on genetically-engineered, human NK cells bearing multiple anti-tumor functions, including local tumor responsiveness, that addresses key drivers of GBM resistance to therapy: antigen escape, poor immune cell homing, and immunometabolic reprogramming of immune responses. We engineered dual-specific CAR-NK cells to bear a third functional moiety that is activated in the GBM TME and addresses immunometabolic suppression of NK cell function: a tumor-specific, locally-released antibody fragment which can inhibit the activity of CD73 independently of CAR signaling and decrease the local concentration of adenosine. The multifunctional human NK cells targeted patient-derived GBM xenografts, demonstrated local tumor site specific activity in the tissue and potently suppressed adenosine production. We also unveil a complex reorganization of the immunological profile of GBM induced by inhibiting autophagy. Pharmacologic impairment of the autophagic process not only sensitized GBM to antigenic targeting by NK cells, but promoted a chemotactic profile favorable to NK infiltration. Taken together, our study demonstrates a promising new NK cell-based combinatorial strategy that can target multiple clinically-recognized mechanisms of GBM progression simultaneously
    corecore