Synthetic biology approaches for enhancing safety and specificity of CAR-T cell therapies for solid cancers.

CAR-T cell therapies have been successful in treating numerous hematologic malignancies as the T cell can be engineered to target a specific antigen associated with the disease. However, translating CAR-T cell therapies for solid cancers is proving more challenging due to the lack of truly tumor-associated antigens and the high risk of off-target toxicities. To combat this, numerous synthetic biology mechanisms are being incorporated to create safer and more specific CAR-T cells that can be spatiotemporally controlled with increased precision. Here, we seek to summarize and analyze the advancements for CAR-T cell therapies with respect to clinical implementation, from the perspective of synthetic biology and immunology. This review should serve as a resource for further investigation and growth within the field of personalized cellular therapies.

Paraxial full-field cloaking.

We complete the 'paraxial' (small-angle) ray optics cloaking formalism presented previously [Opt. Express 22, 29465 (2014)], by extending it to the full-field of light. Omnidirectionality is then the only relaxed parameter of what may be considered an ideal, broadband, field cloak. We show that an isotropic plate of uniform thickness, with appropriately designed refractive index and dispersion, can match the phase over the whole visible spectrum. Our results support the fundamental limits on cloaking for broadband vs. omnidirectionality, and provide insights into when anisotropy may be required.

Paraxial ray optics cloaking.

Despite much interest and progress in optical spatial cloaking, a three-dimensional (3D), transmitting, continuously multidirectional cloak in the visible regime has not yet been demonstrated. Here we experimentally demonstrate such a cloak using ray optics, albeit with some edge effects. Our device requires no new materials, uses isotropic off-the-shelf optics, scales easily to cloak arbitrarily large objects, and is as broadband as the choice of optical material, all of which have been challenges for current cloaking schemes. In addition, we provide a concise formalism that quantifies and produces perfect optical cloaks in the small-angle ('paraxial') limit.

Amplitude-only, passive, broadband, optical spatial cloaking of very large objects.

We demonstrate three amplitude cloaks that can hide very large spatial objects over the entire visible spectrum using only passive, off-the-shelf optics. The cloaked region for all of the devices exceeds 106 mm³, with the largest exceeding 108 mm³. Although unidirectional, these cloaks can hide the cloaked object, even if the object is transversely illuminated or self-illuminated. Due to the small usable solid angle, but simple scaling, these cloaks may be of value in hiding small field-of-view objects such as mid- to high-earth orbit satellites from earth-based observation. Active phase front manipulation can also make these cloaks invisible to some forms of image homodyning.

A comparative study of diagnostic accuracy in 3026 pleural biopsies and matched pleural effusion cytology with clinical correlation.

BACKGROUND: Pleural effusion can be caused by a wide range of benign and malignant conditions. Pleural biopsy and effusion cytology represent two key methods of pathological diagnosis. To compare the performance these two methods, a large cohort of matched pleural biopsy and effusion cytology with clinical follow-up was reviewed. METHODS: Pleural biopsies and effusion cytology specimens over a period of 18 years were retrieved. Cytology specimens collected within 7 days of pleural biopsy were matched. Reports were reviewed, and the cause for pleural effusion was determined by hospital disease coding and clinical data. RESULTS: Totally, 3026 cases were included. The leading cause of benign effusion was tuberculosis (n = 650). Malignant pleural effusion (MPE) was more common in older females (p < 0.001) and mostly due to lung cancer (n = 959), breast cancer (n = 64), and mesothelioma (n = 48). The inadequate/insufficient (B1/C1) rate of biopsy was higher than cytology (15.6% vs. 0.3%) but the rates for other diagnostic categories were similar. Biopsy and cytology showed a correlation coefficient of 0.315, improving to 0.449 when inadequate/insufficient (B1/C1) cases were excluded. The ROM for benign cytology (C2) was lower than biopsy (B2) (p < 0.001). Compared with biopsy, the diagnostic accuracy was higher in cytology overall and for metastatic carcinomas (p < 0.001) but lower for hematolymphoid malignancies (p = 0.014) and mesotheliomas (p = 0.002). CONCLUSIONS: These results suggest that effusion cytology may be better for confirming benignity and diagnosing carcinomatous MPE. In these cases, pleural biopsy may be withheld to reduce procedural risks. However, for suspected hematolymphoid malignancies and mesothelioma, biopsy should be considered.

Physical and Biological Characterization of the Gamma-Irradiated Human Cornea.

PURPOSE: To compare the physical and biological characteristics of commercial gamma-irradiated corneas with those of fresh human corneas and to determine suitability for transplantation. METHODS: The physical properties of gamma-irradiated and fresh corneas were evaluated with respect to light transmittance, hydration (swelling ratio), elastic modulus (compressive modulus by the indentation method), matrix organization (differential scanning calorimetry), and morphology (light and transmission electron microscopy). The biological properties of the gamma-irradiated cornea, including residual cell content and cellular biocompatibility, were evaluated by quantifying DNA content and measuring the proliferation rate of human corneal epithelial cells, respectively. RESULTS: The hydration, light transmittance, elastic modulus, and proliferation rate of human corneal epithelial cells were not significantly different between fresh and gamma-irradiated corneas. However, differences were observed in tissue morphology, DNA content, and thermal properties. The density of collagen fibrils of the gamma-irradiated corneal sample (160.6 ± 33.2 fibrils/µm) was significantly lower than that of the fresh corneal sample (310.0 ± 44.7 fibrils/µm). Additionally, in the gamma-irradiated corneas, cell fragments-but not viable cells-were observed, supported by lower DNA content of the gamma-irradiated cornea (1.0 ± 0.1 µg/mg) than in fresh corneas (1.9 µg/mg). Moreover, the denaturation temperature of gamma-irradiated corneas (61.8 ± 1.1 °C) was significantly lower than that of fresh corneas (66.1 ± 1.9 °C). CONCLUSIONS: Despite structural changes due to irradiation, the physical and biological properties of the gamma-irradiated cornea remain similar to the fresh cornea. These factors, combined with a decreased risk of rejection and longer shelf life, make the gamma-irradiated tissue a viable and clinically desired option in various ophthalmic procedures.

Application of a collagen-based membrane and chondroitin sulfate-based hydrogel adhesive for the potential repair of severe ocular surface injuries.

This study was performed to evaluate the potential of a chondroitin sulfate-polyethylene glycol (CS-PEG) adhesive and collagen-based membrane (collagen vitrigel, CV) combination as a method to treat penetrating ocular injuries on the battlefield and to improve this method with two technologies: an antibiotic releasing CS-PEG adhesive and a corneal shaped CV. Burst testing using porcine cadaveric eyes, high-performance liquid chromatography, the Kirby-Bauer bacterial inhibition test, and CV implantations on the live and cadaveric rabbit eyes were performed. The ocular burst test showed CS-PEG adhesive could successfully repair 5-mm to 6-mm length wounds in the corneal and corneoscleral regions but would require CS-PEG + CV to treat larger wounds similar to those seen on the battlefield. In addition, high performance liquid chromatography and the Kirby-Bauer bacterial inhibition test presented evidence suggesting the vancomycin incorporated CS-PEG could inhibit Staphylococcus infection for 9 days. Furthermore, the curved CV showed an advantage by matching the corneal contour without any wrinkle formation. Although this pilot study showed a limited range of possible applications, we demonstrated that the combination of CS-PEG adhesive + CV is a promising method and the 2 technologies improve their applicability to the special demands of the battlefield.