Engineered red blood cells (activating antigen carriers) drive potent T cell responses and tumor regression in mice.

Activation of T cell responses is essential for effective tumor clearance; however, inducing targeted, potent antigen presentation to stimulate T cell responses remains challenging. We generated Activating Antigen Carriers (AACs) by engineering red blood cells (RBCs) to encapsulate relevant tumor antigens and the adjuvant polyinosinic-polycytidylic acid (poly I:C), for use as a tumor-specific cancer vaccine. The processing method and conditions used to create the AACs promote phosphatidylserine exposure on RBCs and thus harness the natural process of aged RBC clearance to enable targeting of the AACs to endogenous professional antigen presenting cells (APCs) without the use of chemicals or viral vectors. AAC uptake, antigen processing, and presentation by APCs drive antigen-specific activation of T cells, both in mouse in vivo and human in vitro systems, promoting polyfunctionality of CD8+ T cells and, in a tumor model, driving high levels of antigen-specific CD8+ T cell infiltration and tumor killing. The efficacy of AAC therapy was further enhanced by combination with the chemotherapeutic agent Cisplatin. In summary, these findings support AACs as a potential vector-free immunotherapy strategy to enable potent antigen presentation and T cell stimulation by endogenous APCs with broad therapeutic potential.

Microneedle-based device for the one-step painless collection of capillary blood samples.

The advancement of point-of-care diagnostics and the decentralization of healthcare have created a need for the simple, safe, standardized and painless collection of blood specimens. Here, we describe the design and implementation of a capillary blood-collection device that is more convenient and less painful than a fingerstick and venepuncture, and collects 100 µl of blood. The technology integrates into a compact, self-contained device an array of solid microneedles, a high-velocity insertion mechanism, stored vacuum, and a microfluidic system containing lithium heparin anticoagulant. The use of the device requires minimal training, as blood collection is initiated by the single push of a button. In a clinical study involving 144 participants, haemoglobin A1c measurements from device-collected samples and from venous blood samples were equivalent, and the pain associated with the device was significantly less than that associated with venepuncture. The device, which has received premarket clearance by the US Food and Drug Administration, should help improve access to healthcare, and support healthcare decentralization.

Developer's and user's guide to Clotho v2.0 A software platform for the creation of synthetic biological systems.

To design the complex systems that synthetic biologists propose to create, software tools must be developed. Critical to success is the enablement of collaboration across our community such that individual tools that perform specific tasks combine with other tools to provide multiplicative benefits. This will require standardization of the form of the data that exists within the field (Parts, Strains, measurements, etc.), a software environment that enables communication between tools, and a sharing mechanism for distributing the tools. Additionally, this data model must describe the data in a sufficiently rigorous and validated form such that meaningful layers of abstraction can be built upon the base. Herein, we describe a software platform called "Clotho" which provides such a data model, and the plugin and sharing mechanisms needed for a rich tool environment. This document provides a tutorial for users of Clotho and information for software developers who wish to contribute new tools (known as "Apps") to it.