Provided are nucleic acid constructs, Toxoplasma comprising same, pharmaceutical compositions comprising same and methods using same for delivering a protein-of-interest to a tissue-of-interest of a subject, such as the CNS and further treating a pathology which is treatable by administration of a therapeutic polypeptide in a central nervous system of the subject.

The present disclosure provides fusion proteins comprising Mycobacterium tuberculosis (Mtb) antigens, nucleic acid molecules encoding the same, vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.

The present application relates to a chimeric antigen receptor (CAR) which comprises a target-dependent on-switch CAR. The CAR of the invention may reduce cytotoxicity towards normal cells and improve CAR-T safety. CAR molecules were designed using the transmembrane and juxtamembrane motifs of the IL2 receptor β chain (IL2Rβ or IL2Rb), the L ow-Density Lipoprotein Receptor (LDLR), the Seizure 6-like Protein 2 (SEZ6L2), and degradation sequence (PSKFFSQL) of IL2Rβ, which resulted in greatly reduced CAR expression at the cell surface in the absence of target antigen, while retaining downstream activation ability in response to antigen-expressing target cells. In the absence of target antigen, CAR surface expression is undetectable. The present application has shown that primary T cells expressing these surface-unstable CAR variants are able to elicit antigen-dependent target cell killing. By limiting CAR activity in this way, the present application can reduce therapeutic toxicity and T cell exhaustion. Due to its limited detectability in the absence of antigen, the present application refers to this system as a “Stealth CAR”. The present application further relates to compositions, preparation methods and uses of the Stealth CAR of the present application.

AXL-specific antibodies and uses therefor are described, including monoclonal and single domain antibodies. Such antibodies bind to cell surface expressed human AXL at an epitope in an immunoglobulin-like (IgL) domain of the AXL ectodomain. The antibody may be used in an antibody-drug conjugate (ADC), for example in the treatment, detection or staging of cancer. The antibody may be biparatopic.

The present invention relates to a method for identifying specific binding partners (e.g. antibodies or antibody mimetics) which bind to a desired target polypeptide. In particular, the method involves expressing a library of specific binding partners in a population of mammalian cells, wherein each cell in the population of cells displays the target polypeptide on the outer surface of the cell, and identifying or isolating cells within the population of cells to which specific binding partners are bound.

Compositions, methods, and systems for modifying sterol metabolism in a subject is disclosed. In some embodiments, the subjects may be administered one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium. In many embodiments, the cell is a macrophage or monocyte stably expressing three or more enzymes that aid in opening the β ring of cholesterol. The disclosed compositions and methods may be useful in lowering cholesterol levels in a subject in need thereof. In some embodiments, the subject may have a genetic predisposition to atherosclerosis.

The present disclosure provides gene therapy vectors comprising a polynucleotide sequence encoding a LAMP-2 polypeptide, methods of use thereof, pharmaceutical compositions, and more. In particular, the disclosure provides recombinant AAV vectors having AAVrh74 serotype expressing LAMP-2A, LAMP-2B, or LAMP-2C for use as a therapeutic in, for example, Danon Disease.

The presently disclosed subject matter provides antibodies that bind to B-cell maturation antigen (BCMA) and methods of using the same.

The present invention provides a recombinant exosome and uses thereof. More particularly, the present invention provides a recombinant exosome wherein a phagocytosis promoting protein is presented on the surface thereof.

The invention provides a tandemly repeated protein comprising at least two repeats of an amino acid sequence of an antibody binding protein or a fragment thereof and a cell having the repeats expressed on the membrane thereof, which can be used in immunoassay to improve detection sensitivity and detection limit.