The present invention provides an intraceptor that interacts with and decreases activity of with VEGF and/or a VEGFR for the treatment of angiogenesis-related conditions. The present invention further provides pharmaceutical compositions, and methods of use thereof for the treatment and prevention of an angiogenesis-related condition using said intraceptors. The invention further provides for nucleic acids encoding said intraceptors.

The present invention relates to Shiga toxin effector polypeptides with reduced antigenic and/or immunogenic potential. Immunogenicity can be a limitation for the repeated administration to mammals of proteins and polypeptides derived from Shiga toxins. The Shiga toxin effector polypeptides of the present invention have uses as components of therapeutics, diagnostics, and immunization materials. The cytotoxic proteins of the present invention have uses for selective killing of specific cell types and as therapeutics for the treatment of a variety of diseases, including cancers, immune disorders, and microbial infections. The proteins of the present invention also have uses for detecting specific cell types, collecting diagnostic information, and monitoring the treatment of a variety of diseases, such as, e.g., cancers, immune disorders, and microbial infections.

The present disclosure provides opsins, including variant opsins with increased activity and/or increased trafficking to the plasma membrane. The opsins are useful in therapeutic and screening applications, which are also provided.

The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which X is a nucleic acid sequence which encodes a cleavage site; and A and B are nucleic acid sequences encoding a first and a second chimeric antigen receptor (CAR), each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens; wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain; and wherein: (a) the first and/or second CAR comprises an intracellular retention signal; and/or (b) the signal peptide of the first or second CAR comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.

The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which A and B are nucleic acid sequences encoding a first and a second polypeptide of interest (POI); and X is a nucleic acid sequence which encodes a cleavage site, wherein either the first or second POI is a transmembrane protein which comprises an intracellular retention signal.

Provided are methods of selecting for cells that comprise two or more separate expression constructs. In certain embodiments, the methods comprise contacting a population of cells with two or more separate expression constructs under conditions in which the two or more expression constructs are delivered to cells of the population of cells. The two or more separate expression constructs comprise a first expression construct that encodes a fusion protein comprising a selection marker, a protein localization tag, and a protease cleavage site disposed between the selection marker and the protein localization tag. The second expression construct encodes a protein required for cell surface expression of the selection marker. Such methods further comprise selecting for cells exhibiting cell surface expression of the selection marker. Related cells, compositions, kits and therapeutic methods are also provided.

Provided are NK-92 cells expressing a chimeric antigen receptor (CAR). The CAR can comprise an intracellular domain of FcRI. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer or a viral infection, comprising administering to the patient NK-92-CAR cells.

The invention relates to protein-based T-cell receptor knockdown, and its use in T-cell therapies.

A fusion protein for use as a hepatitis B therapeutic vaccine is disclosed. The fusion protein comprises: (a) an antigen-presenting cell (APC)-binding domain or a CD91 receptor-binding domain; (b) a protein transduction domain; and (c) an antigen comprising a hepatitis B virus X protein deletion mutant that lacks amino acids (aa) at least from as 21 to as 50. The protein transduction domain is a fusion polypeptide comprising a T cell sensitizing signal-transducing peptide, a linker, and a translocation peptide. The APC-binding domain or the CD91 receptor-binding domain is located at the N-terminus of the fusion protein, and the antigen is located at the C-terminus of the protein transduction domain.

The present disclosure provides opsins, including variant opsins with increased activity and/or increased trafficking to the plasma membrane. The opsins are useful in therapeutic and screening applications, which are also provided.