The present disclosure provides use of chemokine receptor CXCR5, wherein CAR-T cells with enhanced chemotaxis are obtained by modifying chimeric antigen receptor T cells (CAR-T cells) utilizing the chemotactic signal between CXCR5 and its ligand CXCL13. The chemokine receptor CXCR5 can guide CAR-T cells to migrate to tumors. It has an excellent ability to enhance the chemotaxis of CAR-T cells, can specifically clear tumor cells, and effectively solve the problem of poor efficacy of the existing CAR-T therapy for solid tumors, thereby exhibiting broad application prospects and great market value.

Provided herein are compositions and methods for the treatment of a disease, such as cancer, using a chimeric antigen receptor or genetically-modified cells comprising a chimeric antigen receptor having specificity for CD20. The invention provides polynucleotides encoding such chimeric antigen receptors, and genetically-modified cells comprising such chimeric antigen receptors. Also provided are methods for making such genetically-modified cells and pharmaceutical compositions comprising the same. The invention further provides methods for treating a disease (e.g., cancer) in a subject by administering such genetically-modified cells or compositions. The main embodiments concern CARs with an scFv specific for CD20, the hinge and transmembrane domains from CD8, the costimulatory cytoplasmic or signalling domain from co-stimulatory molecules Novell (N1) or Novel6 (N6) and the CD3zeta intracellular signaling domain.

Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, the expansion employing a feeder cell population.

The present invention relates to a composition for preventing or treating cancer, the composition containing IL-2 surface expression-extracellular vesicles as an active ingredient. According to the present invention, immune cells, in which useful cytokines have been expressed on the cell surface, and extracellular vesicles, preferably small extracellular vesicles (sEV), which are derived from the immune cells and have useful cytokines expressed on the surface were prepared using a lentiviral vector containing a cytokine-linker-a PDGF receptor transmembrane domain, and it was found that the extracellular vesicles increased proliferation and activity of cytotoxic T cells thereby increasing anti-cancer immune efficacy. Thus, the extracellular vesicles having the efficacy can be usefully utilized as a pharmaceutical composition for preventing or treating cancer, a pharmaceutical composition for co-administration with an anticancer drug, or a composition for delivering a drug or a physiologically active material.

Provided herein are CD70 targeting chimeric antigen receptors and engineered immune cells (e.g., T cells) comprising such CAR. Method of treating a cancer expressing CD70 using such engineered immune cells are also provided. In some embodiments, the method of treating cancer further comprising using an agent that enhances CD70 expression in the cancer (e.g., azacitidine) in combination with the engineered immune cells comprising the CD70-targeting CAR.

A factor that is caused by a nucleic acid and influences the kinetics of an extracellular vesicle is screened. A library of barcoded extracellular vesicles is provided.

Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a codon optimized new generation regulatable fusogenic oncolytic herpes simplex virus-1 that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of solid tumors, as well as other cancers.

Disclosed are nucleic acid constructs comprising a promoter; a nucleic acid sequence encoding a single-chain variable fragment (scFv); a nucleic acid sequence encoding a notch transmembrane domain; and a nucleic acid sequence encoding a transcription factor. Disclosed are vectors comprising any of the disclosed nucleic acid constructs. Disclosed are proteins comprising a scFv; a notch transmembrane domain; and a transcription activator. Disclosed are methods of increasing human leukocyte antigen class I (HLA-I) on the surface of a tumor cell in a subject comprising administering to the subject one or more of the recombinant cells or compositions comprising a recombinant cell disclosed herein.

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.

Methods and compositions are described that can be used as a pre-treatment for HIV therapies.