The future of affordable cancer immunotherapy

The treatment of cancer was revolutionized within the last two decades by utilizing the mechanism of the immune system against malignant tissue in so-called cancer immunotherapy. Two main developments boosted cancer immunotherapy: 1) the use of checkpoint inhibitors, which are characterized by a relatively high response rate mainly in solid tumors; however, at the cost of serious side effects, and 2) the use of chimeric antigen receptor (CAR)-T cells, which were shown to be very efficient in the treatment of hematologic malignancies, but failed to show high clinical effectiveness in solid tumors until now. In addition, active immunization against individual tumors is emerging, and the first products have reached clinical approval. These new treatment options are very cost-intensive and are not financially compensated by health insurance in many countries. Hence, strategies must be developed to make cancer immunotherapy affordable and to improve the cost-benefit ratio. In this review, we discuss the following strategies: 1) to leverage the antigenicity of “cold tumors” with affordable reagents, 2) to use microbiome-based products as markers or therapeutics, 3) to apply measures that make adoptive cell therapy (ACT) cheaper, e.g., the use of off-the-shelf products, 4) to use immunotherapies that offer cheaper platforms, such as RNA- or peptide-based vaccines and vaccines that use shared or common antigens instead of highly personal antigens, 5) to use a small set of predictive biomarkers instead of the “sequence everything” approach, and 6) to explore affordable immunohistochemistry markers that may direct individual therapies

The Great Imitator on the Rise: Optic Disc Involvement in Syphilis Patients

Syphilis is an infectious venereal disease caused by the spirochete Treponema pallidum. Ocular manifestations, are reported in the literature in 2-10% of the cases can occur at any stage of the disease and may involve any ocular structure. During the last decade the number of syphilis cases has been on the rise in developed countries. As a result, ocular syphilis has become more common too. The purpose of this study was to report the current incidence and characteristics of optic nerve involvement in patients with newly diagnosed syphilis

Single‐cell transcriptomics reveals a senescence‐associated IL‐6/CCR6 axis driving radiodermatitis

Abstract Irradiation‐induced alopecia and dermatitis (IRIAD) are two of the most visually recognized complications of radiotherapy, of which the molecular and cellular basis remains largely unclear. By combining scRNA‐seq analysis of whole skin‐derived irradiated cells with genetic ablation and molecular inhibition studies, we show that senescence‐associated IL‐6 and IL‐1 signaling, together with IL‐17 upregulation and CCR6+‐mediated immune cell migration, are crucial drivers of IRIAD. Bioinformatics analysis colocalized irradiation‐induced IL‐6 signaling with senescence pathway upregulation largely within epidermal hair follicles, basal keratinocytes, and dermal fibroblasts. Loss of cytokine signaling by genetic ablation in IL‐6−/− or IL‐1R−/− mice, or by molecular blockade, strongly ameliorated IRIAD, as did deficiency of CCL20/CCR6‐mediated immune cell migration in CCR6−/− mice. Moreover, IL‐6 deficiency strongly reduced IL‐17, IL‐22, CCL20, and CCR6 upregulation, whereas CCR6 deficiency reciprocally diminished IL‐6, IL‐17, CCL3, and MHC upregulation, suggesting that proximity‐dependent cellular cross talk promotes IRIAD. Therapeutically, topical application of Janus kinase blockers or inhibition of T‐cell activation by cyclosporine effectively reduced IRIAD, suggesting the potential of targeted approaches for the treatment of dermal side effects in radiotherapy patients

Further Evidence of Inadequate Quality in Lateral Flow Devices Commercially Offered for the Diagnosis of Rabies

As a neglected zoonotic disease, rabies causes approximately 5.9 × 104 human deaths annually, primarily affecting low- and middle-income countries in Asia and Africa. In those regions, insufficient surveillance is hampering adequate medical intervention and is driving the vicious cycle of neglect. Where resources to provide laboratory disease confirmation are limited, there is a need for user-friendly and low-cost reliable diagnostic tools that do not rely on specialized laboratory facilities. Lateral flow devices (LFD) offer an alternative to conventional diagnostic methods and may strengthen control efforts in low-resource settings. Five different commercially available LFDs were compared in a multi-centered study with respect to their diagnostic sensitivity and their agreement with standard rabies diagnostic techniques. Our evaluation was conducted by several international reference laboratories using a broad panel of samples. The overall sensitivities ranged from 0% up to 62%, depending on the LFD manufacturer, with substantial variation between the different laboratories. Samples with high antigen content and high relative viral load tended to test positive more often in the Anigen/Bionote test, the latter being the one with the best performance. Still, the overall unsatisfactory findings corroborate a previous study and indicate a persistent lack of appropriate test validation and quality control. At present, the tested kits are not suitable for in-field use for rabies diagnosis, especially not for suspect animals where human contact has been identified, as an incorrect negative diagnosis may result in human casualties. This study points out the discrepancy between the enormous need for such a diagnostic tool on the one hand, and on the other hand, a number of already existing tests that are not yet ready for use.</jats:p

Sol-Gel Deposition of Iridium Oxide for Biomedical Micro-Devices

Flexible iridium oxide (IrOx)-based micro-electrodes were fabricated on flexible polyimide substrates using a sol-gel deposition process for utilization as integrated pseudo-reference electrodes for bio-electrochemical sensing applications. The fabrication method yields reliable miniature on-probe IrOx electrodes with long lifetime, high stability and repeatability. Such sensors can be used for long-term measurements. Various dimensions of sol-gel iridium oxide electrodes including 1 mm × 1 mm, 500 µm × 500 µm, and 100 µm × 100 µm were fabricated. Sensor longevity and pH dependence were investigated by immersing the electrodes in hydrochloric acid, fetal bovine serum (FBS), and sodium hydroxide solutions for 30 days. Less pH dependent responses, compared to IrOx electrodes fabricated by electrochemical deposition processes, were measured at 58.8 ± 0.4 mV/pH, 53.8 ± 1.3 mV/pH and 48 ± 0.6 mV/pH, respectively. The on-probe IrOx pseudo-reference electrodes were utilized for dopamine sensing. The baseline responses of the sensors were higher than the one using an external Ag/AgCl reference electrode. Using IrOx reference electrodes integrated on the same probe with working electrodes eliminated the use of cytotoxic Ag/AgCl reference electrode without loss in sensitivity. This enables employing such sensors in long-term recording of concentrations of neurotransmitters in central nervous systems of animals and humans