Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

The present invention pertains to an inventive release mechanism for extracellular vesicle (EV)-mediated intracellular and intramembrane delivery of therapeutic polypeptides. More specifically, the invention relates to EVs comprising polypeptide constructs which comprise a therapeutic polypeptide releasably attached to an exosomal polypeptide. Furthermore, the present invention pertains to manufacturing methods, pharmaceutical compositions, medical uses and applications, and various other embodiments related to the inventive EVs.

The present invention relates generally to methods and compositions for gene therapy and immunotherapy that activate gamma delta T-cells, and in particular, can be used in the treatment of various cancers and infectious diseases.

Provided are methods and compositions to target delivery of cells to a tissue lesion, thereby treating the lesion. For example, biotinylated antibodies with affinity to a lesion epitope are administered at the lesion. Reparative cells including avidin and biotin are then administered at the lesion. The reparative cells are targeted to the lesion via avidin-biotin bridges to the antibodies, with additional cells recruited to the lesion via cell-to-cell avidin-biotin bridges. In certain examples, antibody-reparative cell complexes are formed by mixing the biotinylated antibodies with the reparative cells including avidin and biotin. The complexes are then administered at the lesion. In other examples, multivalent antibodies are used to target reparative cells to the lesion, such as by binding an epitope at the lesion and an epitope present on the reparative cell. In other examples, the antibodies are chemically linked to a reparative cell or to a nanosome containing a therapeutic agent.

This disclosure pertains to pharmaceutical compositions of aerosolized compositions containing mitochondria, methods of preparing and using the compositions, and devices for administering the compositions.

Provided herein are methods of treating a tumor comprising administering (i) a composition comprising an extracellular vesicle and a STING agonist, e.g., exosome encapsulating STING agonists, in combination with (ii) an IL-12 moiety.

The present disclosure relates to a composition for the use in the fields of cancer, immunotherapy and biotechnology. Particularly it relates to the field of gellan gum hydrogel-like particles for artificial antigen presentation in immunotherapy.

Provided herein are cell surface conjugates containing a cell surface molecule and at least one agent, such as at least one affinity tag, and engineered cells expressing such cell surface conjugates. In some embodiments, the cell surface molecule does not contain an intracellular signaling domain or is not capable of mediating intracellular signaling. In some embodiments, the cells engineered to contain the cell surface conjugate, such as T cells, further contain a genetically engineered recombinant receptor that specifically binds to antigens, such as a chimeric antigen receptor (CAR). Also provided are methods of detecting, identifying, selecting or targeting cells expressing the cell surface conjugates, such as in connection with methods of manufacturing engineered cells or in connection with administration of such cells to subjects, including methods of adoptive cell therapy.

In one aspect, methods of targeted nanoparticles and cell delivery are described herein. In some embodiments methods described herein comprise coupling nanoparticles and cells to a carrier cell to form a nanoparticle-cell conjugate or cell-cell conjugate, disposing the nanoparticle-cell or cell-cell conjugate in a biological environment, and delivering the nanoparticles and cells to target cells or tissues located within the biological environment. The nanoparticles comprise a biodegradable photoluminescent polymer, and the nanoparticle-cell conjugate is formed using one or more click chemistry reaction products.

The present disclosure provides compositions and methods relating to the use of platelet microparticles to deliver therapeutic antibodies. In particular, the present disclosure provides novel compositions and methods for treating cardiac injury using anti-IL-1β platelet microparticles (IL1-PMs) to promote cardiac detoxification and repair after cardiac injury (e.g., myocardial infarction).