An immunoresponsive cell, such as a T-cell expressing a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and g) a binding element that specifically interacts with a second epitope on a target antigen. This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

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.

Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

A specific recombinant humanized monoclonal antibody targeting human GPRC5D can be used in ELISA and flow detection methods, and can be used for diagnosis and treatment targeting GPRC5D protein. The monoclonal antibody comprises a heavy chain variable region and a light chain variable region, and the amino acid sequence and nucleotide sequence of the monoclonal antibody can be used alone or in double-stranded combination. In addition, the sequences of the specific recombinant humanized monoclonal antibody targeting human GPRC5D can be constructed into biological materials or preparations such as monoclonal antibodies, antibody conjugates, bispecific antibodies, CAR-immune cells, etc., and can be used for the diagnosis and treatment of GPRC5D-related diseases.

This invention relates synthetic T cell receptor molecules and methods of making and using the same.

Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from a CD33 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders such as acute myeloid leukemia (AML), and relapsed or refractory AML.

The present disclosure provides anti-LILRB4 antibodies or antigen-binding fragments thereof, anti-LILRB4 chimeric antigen receptor protein, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and the uses thereof.

The present disclosure provides compositions and methods for treating diseases associated with expression of CD19 and/or CD22, e.g., by administering a recombinant T cell or natural killer (NK) cell comprising a CD22 CAR and a CD19 CAR as described herein. The disclosure also relates to CAR molecules specific to CD22 and/or CD19, methods of making a cell comprising the same and vectors encoding the same.

The presently disclosed subject matter provides methods and compositions for enhancing immune responses toward tumor and pathogen antigens. It relates to fusion polypeptide that can be expressed in cells (e.g., immunoresponsive cells comprising an antigen-recognizing receptor) to improve the activity and/or efficiency of the cells. In certain embodiments, the fusion polypeptide comprises an extracellular domain comprising an antigen-binding fragment and a co-stimulatory ligand polypeptide, and an intracellular domain comprising a first co-stimulatory molecule polypeptide.

Chimeric antigen receptors targeting both BAFF-R and CD19 are described as are methods for their use.