Provided herein are chimeric antigen receptor (CAR) viral libraries and methods of making the same. In some embodiments, the CAR comprises an intracellular domain (ICD) with at least one immune activation signaling domain, one co-stimulatory domain, and one or more inhibitory signaling domain or signaling domain from non-T cell lineages. In some embodiments, the signaling domains of the ICD are joined by distinct linkers of 10 amino acids. In some embodiments, the CARs contain a 18-nucleotide barcode in the 3 untranslated region. Also provided herein, are CAR cell libraries and methods of making the same.

Described herein are programmable tropism virus-like particles (ptVLPs), comprising a membrane comprising a phospholipid bilayer with one or more wild-type or mutant/truncated virus-derived glycoproteins on the external side. The virus-derived envelope glycoprotein(s) can optionally be fused directly to a targeting domain (e.g., peptide, single chain variable fragment (scFv), nanobody, fibronectin type 3 domain (FN3), arginylglycylaspartic acid motif (RGD), single variable domain on a heavy chain/nanobody (VHH), variable domain of new antigen receptor (VNAR), darpin, or other targeting ligand), and/or can be present in combination with a membrane-anchored targeting domain. A biomolecule cargo (preferably fused to a membrane recruitment domain, such as a Pleckstrin homology domain) can be disposed in the core of the ptVLP. Preferably, the ptVLP does not comprise a protein from any human endogenous or exogenous viral gag, pro, pol, or other viral proteins that reside inside of enveloped particles.

Disclosed herein is a recombinant protein including botulinum toxin and cell penetrating peptides and cosmetic composition. The cell penetrating peptide according to the present disclosure may be actively used as a topical agent for various disease treatment, aesthetic, or cosmetic purposes, especially for a cosmetic composition, by securing better convenience as well as maximizing the intrinsic in vivo efficacy of the botulinum toxin through the cell penetrating recombinant proteins that combines the botulinum toxin and a cell penetrating peptide by making skin penetration and/or cell penetration for botulinum toxin more efficient.

A nucleic acid construct and mammalian cell harboring nucleic acids encoding an anti-CD7 chimeric antigen receptor are provided. Methods for treating cancer, in particular a hematologic cancer, using the nucleic acid construct or mammalian cell are also described.

The present invention relates to a combination comprising at least fusion protein comprising a binding protein specifically recognizing a cancer-related antigen and an inflammatory cytokine, and a chimeric antigen receptor (CAR)-T cell recognizing a cancer-related antigen.

Provided herein, in some embodiments, are antibodies, antigen-binding antibody fragments, chimeric antigen receptors (CARs) and bispecific T cell engagers (BiTEs) that bind specifically to B7 homolog 6. Also provided herein are methods of using the same and cells comprising the same.

Multi-specific antigen-binding constructs that target immunotherapeutics are described. The multi-specific antigen-binding constructs comprise a first antigen-binding polypeptide construct that binds to an immunotherapeutic (such as a CAR-T cell or a bispecific T-cell engager), and a second antigen binding polypeptide construct that binds to a tumour-associated antigen. Also described are methods of using the multi-specific antigen-binding constructs to re-direct or enhance the binding of the immunotherapeutic to a tumour cell, and methods of treating patients who have relapsed from or failed treatment with the immunotherapeutic.

This invention provides biosensors, cell models, and methods of their use for monitoring chloride ion, where the biosensors can include targeting domains, sensing domains and reporting domains. Biosensors can be introduced into cells reprogrammed to represent experimental or pathologic cells of interest, including as detectors of chloride ions, as TempoChloro accomplishes.

The present application provides PEI compounds comprising a linker, PEI-polypeptide conjugates (e.g., PEI-antibody conjugates), and complexes thereof comprising a biologically active molecule. Methods of preparing and using the compounds, conjugates and complexes are further provided. The PEI-polypeptide conjugates and complexes are useful for delivering biologically active molecules to the cytoplasm of cells and promoting release of the biologically active molecules from the endo-lysosomal pathway.

Disclosed are compositions and methods for targeted treatment of CD33-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill CD33-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a CD33-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs. Also disclosed are multivalent antibodies are disclosed that are able to engage T-cells to destroy CD33-expressing malignant cells.