The methods and compositions described herein address the need in the art by providing compositions and methods for a therapy with an antibody that is specifically targeted to and/or retained intra- or peri-tumorally, limiting systemic exposure and reducing side-effects. Accordingly, aspects of the disclosure relate to a composition comprising an immunotherapeutic antibody operatively linked to an extracellular matrix (ECM)-affinity peptide. An ECM-affinity peptide is one that has affinity for an extracellular matrix protein.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.

The present disclosure provides adoptive T cell therapies that have improved DARIC architectures for targeting tumor antigens and recruiting TCR signaling complexes for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which A is nucleic acid sequence encoding a first polypeptide which comprises a first signal peptide; B is nucleic acid sequence encoding a second polypeptide which comprises a second signal peptide and X is a nucleic acid sequence which encodes a cleavage site, wherein the first signal peptide or the second signal peptide comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.

Described herein is a chimeric costimulatory receptor (CCR) molecule having an extracellular domain of a Tumor Necrosis Factor Superfamily member, a transmembrane domain and a cytosolic costimulatory signaling domain from a Tumor Necrosis Factor Receptor Superfamily member is provided. Also provided are pharmaceutical compositions having a T cell expressing CCR and methods and uses of such T cells to treat cancers.

The present invention provides a mutant RSV F protein having a mutation, wherein the mutation is a substitution of a leucine corresponding to a leucine at position 141 of an amino acid sequence of SEQ ID NO: 1 or a leucine corresponding to a leucine at position 142 with a cysteine, and a substitution of a leucine corresponding to a leucine at position 373 with a cysteine, and a disulfide bond is formed between the cysteines. Further provided is a mutant RSV F protein having a mutation, wherein the mutation is a substitution of a glutamic acid corresponding to a glutamic acid at position 60 of the amino acid sequence of SEQ ID NO: 1 with a non-acidic amino acid.

The disclosure relates to Angiopoietin-1 mimetics for treating vascular diseases via agonistic activation of Tie2/TEK receptor.

The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides novel class 1, Type IV and novel class I, Type I Cas proteins and their use in modifying target sequences.

Compositions and methods are provided for depletion of pluripotent cells. In one embodiment of the invention, methods are provided for depletion of pluripotent cells from a mixed population of differentiated cells and stem cells, to provide a population of cells substantially free of pluripotent stem cells.