IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.

Background: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.

Methods: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant.

Getting better mileage with logically primed CARs.

Although remarkably successful against liquid tumors, chimeric antigen receptor (CAR)-T cell therapy has been stymied by solid tumors, limited by inadequate specificity and poor efficacy. Pairing synthetic Notch (synNotch) receptors with CARs, Choe et al. and Hyrenius-Wittsten et al.

The Protective Effects of Soft Contact Lenses for Contact Sports: A Novel Porcine Model for Corneal Abrasion Biomechanics.

Purpose: The aim of this study was to determine whether soft contact lenses provide protection for the corneal surface.

Methods: Fresh porcine eyes were inflated to intraocular pressures of 11 to 22 mm Hg and secured to a Styrofoam head. Newton meters affixed with artificial acrylic nails were placed at angles of 0°, 45°, and 90° from a porcine corneal surface.

Scleral Fixation of a Toric Lens to Treat Corneal Astigmatism in Eyes without Capsular Support.

Purpose: To describe surgical technique and report short-term visual outcomes after suture-fixation of a single-piece eyelet-toric (SET) intraocular lens (IOL) for treatment of concurrent aphakia and astigmatism.

Design: Retrospective, noncomparative, and non-consecutive case series.

Methods: This was a case series of eleven eyes who underwent successful SET.

Development and Validation of a Natural Language Processing Algorithm to Extract Descriptors of Microbial Keratitis From the Electronic Health Record.

Purpose: The purpose of this article was to develop and validate a natural language processing (NLP) algorithm to extract qualitative descriptors of microbial keratitis (MK) from electronic health records.

Methods: In this retrospective cohort study, patients with MK diagnoses from 2 academic centers were identified using electronic health records. An NLP algorithm was created to extract MK centrality, depth, and thinning.

Navigating CAR-T cells through the solid-tumour microenvironment.

The adoptive transfer of T cells that are engineered to express chimeric antigen receptors (CARs) has shown remarkable success in treating B cell malignancies but only limited efficacy against other cancer types, especially solid tumours. Compared with haematological diseases, solid tumours present a unique set of challenges, including a lack of robustly expressed, tumour-exclusive antigen targets as well as highly immunosuppressive and metabolically challenging tumour microenvironments that limit treatment safety and efficacy. Here, we review protein- and cell-engineering strategies that seek to overcome these obstacles and produce next-generation T cells with enhanced tumour specificity and sustained effector function for the treatment of solid malignancies.

CAR-T design: Elements and their synergistic function.

Chimeric antigen receptor (CAR) T cells use re-engineered cell surface receptors to specifically bind to and lyse oncogenic cells. Two clinically approved CAR-T-cell therapies have significant clinical efficacy in treating CD19-positive B cell cancers. With widespread interest to deploy this immunotherapy to other cancers, there has been great research activity to design new CAR structures to increase the range of targeted cancers and anti-tumor efficacy.

Engineering primary T cells with chimeric antigen receptors for rewired responses to soluble ligands.

The expression of synthetic receptors in primary T cells enables the programming of user-defined responses when designing T-cell therapies. Chimeric antigen receptors (CARs) are synthetic receptors that have demonstrated efficacy in cancer therapy by targeting immobilized antigens on the surface of malignant cells. Recently, we showed they can also rewire T-cell responses to soluble ligands.

CASE OF TORPEDO MACULOPATHY WITH TWO DISTINCT ZONES OF THE RETINAL PIGMENT EPITHELIUM.

Background/purpose: To report a case of torpedo maculopathy with two distinct zones of the retinal pigment epithelium visualized on optical coherence tomography.

Methods: Observational case report.

Results: A 6-year-old female presented for a routine examination.

Natural Language Processing to Quantify Microbial Keratitis Measurements.

A natural language processing (NLP) algorithm to extract microbial keratitis morphology measurements from the electronic health record (EHR) was 75-96% sensitive and 91%-96% specific. NLP accurately extracts data from the corneal exam free-text EHR field.

A Case of Uveitis-Hyphema-Glaucoma Syndrome Due to EX-PRESS Glaucoma Filtration Device Implantation.

Purpose: To report a case of a 69-year-old patient who developed uveitis-glaucoma-hyphema syndrome (UGH) after an uneventful EX-PRESS mini shunt surgery for advanced primary open-angle glaucoma and to discuss management options and clinical implications. UGH syndrome is a rare, but serious complication usually described after cataract surgery. It is often described in anterior chamber intraocular lenses, sulcus lenses, and malpositioned or subluxed lenses resulting in chafing of the lens-iris interface.

TGF-β-responsive CAR-T cells promote anti-tumor immune function.

A chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF-β) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T-cell stimulant. However, clinical translation of TGF-β CAR-T cells for cancer therapy requires the ability to productively combine TGF-β responsiveness with tumor-targeting specificity. Furthermore, the potential concern that contaminating, TGF-β?producing regulatory T (Treg) cells may preferentially expand during TGF-β CAR-T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation.

Liver and spleen volumetry with quantitative MR imaging and dual-space clustering segmentation.

The purpose of this HIPAA-compliant, institutional review board-approved study was to assess the liver and spleen volumes calculated by using a semiautomated dual-space clustering segmentation technique, as compared with the volumes calculated by using the manual contour-tracing method. The quantitative magnetic resonance (MR) imaging data used as input were computed from images acquired by using a mixed fast spin-echo pulse sequence that was implemented with respiratory triggering. Linear regression analysis was used to assess agreement regarding the volumes calculated by using both segmentation techniques.

Tumor necrosis factor alpha activation of the apoptotic cascade in murine articular chondrocytes is associated with the induction of metalloproteinases and specific pro-resorptive factors.

Objective: Tumor necrosis factor alpha (TNFalpha) blockade provides substantive reduction of the symptoms of rheumatoid arthritis (RA). While the biologic actions of TNFalpha have been well characterized in immune and synovial cells, which are known to be major contributors to the progression of cartilage destruction in RA, the current studies were designed to assess the direct effects of TNFalpha on chondrocytes.

Methods: We examined the expression of several groupings of messenger RNA (mRNA) that define key biologic pathways that have previously been associated with either the general actions of TNFalpha or cartilage destruction, in murine articular chondrocytes isolated from wild-type mice and TNFalpha receptor-null (p55/p75(-/-)) mice.