The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

Disclosed are a universal CAR-T cell knocking out one or more of CD3 delta, CD3 gamma, CD3 epsilon and CD3 zeta, and simultaneously introducing the HSV-TK gene. Also disclosed are a method for preparing the above-mentioned CAR-T cell, a preparation comprising the CAR-T cell, and the use of the CAR-T cell.

Provided herein, inter alia, are PD-L1(+) natural killer cells that express soluble IL-15, PD-L1(+) natural killer cells that express soluble IL-15 and truncated EGFR, and methods of treating cancer using the PD-L1(+) natural killer cells. In an aspect is provided a method of treating cancer in a patient in need thereof comprising administering to the patient an effective amount of PD-L1(+) natural killer cells that express soluble IL-15.

The present disclosure relates to immunotherapy. In more specific embodiments, the present disclosure provides systems, compositions, methods and uses of viral vectors comprising nucleic acid sequence of interest that encodes at least one therapeutic product, and a nucleic acid sequence encoding at least one nuclease, for in vivo targeted insertion of the nucleic acid sequence of interest into a target locus within at least one cell of the T lineage.

The presently disclosed subject matter provides novel T cell receptors (TCRs) that target a mutated RAS protooncogene. The presently disclosed subject matter further provides cells comprising such TCRs, and methods of using such cells for treating cancers associated with RAS.

Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.

The present application relates to a CD7-based humanized chimeric antigen receptor and use thereof, specifically a method for constructing chimeric antigen receptor T (CAR-T) cells based on a tumor-specific target CD7 and use thereof in anti-tumor therapy. The chimeric antigen receptor includes an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 signaling domain, which are connected in tandem; where the antigen binding domain binds to a tumor surface antigen, and the tumor surface antigen is CD7. The humanized chimeric antigen receptor of the present application performs particular gene modification on a single-chain antibody specific to an antigen CD7. The modified humanized single-chain antibody has a stronger antigen-antibody binding ability, and the chimeric antigen receptor stimulates T cells better, is maintained longer in vivo, and has a better targeting effect than other CD7 chimeric antigen receptors so that the therapeutic effect of CAR-T cells is enhanced.

Provided herein are antibodies and antigen binding portions thereof that specifically bind receptor tyrosine kinase like orphan receptor 1 (ROR1), various compositions of such antibodies or antigen binding portions thereof, recombinant nucleic acids encoding the antibodies and antigen binding portions thereof, and methods of using the antibodies or antigen-binding portions thereof in cancer therapeutics and diagnostics.

Provided are anti-CD3 antibodies or antigen-binding fragments thereof, isolated polynucleotides encoding the same, pharmaceutical composition comprising the same and the uses thereof.

The present invention pertains to peptide-containing complexes/nanoparticles that are useful for stabilizing and/or delivering one or more molecules of a genome-editing system, such as proteins and/or nucleic acids, for example CRISPR proteins and/or nucleic acids.