The present invention relates to engineered T-cell(s) and methods for using the same as a therapeutic with a potent and selective ability to target an antigen of choice. Engineered T-cells of the disclosure are useful in the treatment of various cancers, infectious diseases, and immune disorders. Also disclosed are methods for expanding engineered and non-engineered T-cell(s) populations to therapeutically useful quantities. An engineered T-cell of the disclosure can be a universal donor, and can be administered to a subject with any MHC haplotype.

The invention relates to a T cell expressing an antibody or comprising the coding sequence of the antibody or an expression vector thereof; the antibody contains an optional signal peptide, an antigen binding sequence and a mutant type Fc segment, wherein the mutant type Fc segment is a Fc segment in which amino acid residues at the 17th site and the 79th site of the IgG4 Fc segment shown by SEQ ID NO: 25 are mutated into E and Q respectively. Preferably, the T cell is a CAR-T cell. The present invention further relates to a treatment application of the T cell in malignant tumors.

Provided herein are recombinant nucleic acids that reduce expression of CD5, CBLB, CISH, DGKA, DGKZ, DNMT3A, MAP4K1, NR4A1, PTPN2, TET2, or ZC3H12A and cells comprising such recombinant nucleic acids. Also provided are methods of making and using such cells.

The present invention provides compositions and methods for generating a genetically modified T cells comprising a chimeric antigen receptor (CAR) having an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the T cell exhibits prolonged exponential expansion in culture that is ligand independent and independent of the addition of exogenous cytokines or feeder cells.

The present invention relates to fusion proteins comprising a chimeric antigen receptor linked to a second polypeptide by a linker domain, wherein the second polypeptide prolongs the surface expression of the CAR, and wherein the linker is a cleavable linker. Also included are nucleic acids encoding the same, methods of treatments, and other methods or uses thereof.

The present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

A chimeric polypeptide, containing a binding peptide that can specifically bind to a target molecule, a receptor regulatory domain containing one or more cleavage sites, and an intracellular domain. The receptor regulatory domain comprises an extracellular region and a transmembrane region, wherein the extracellular region and the transmembrane region are not both derived from a Notch protein. The binding of the binding peptide to the target molecule can induce the cleavage of the receptor regulatory domain, thereby releasing the intracellular domain.

The disclosure provides immune cells comprising a first activator receptor specific to mesothelin and a second inhibitory receptor specific to a ligand that has been lost in a mesothelin-positive cancer cell, and methods of making and using same for the treatment of cancer.

The present invention relates to the field of biomedicine, and in particular, the present invention relates to an antibody or antigen-binding fragment thereof which specifically binds to MSLN, and a chimeric antigen receptor (CAR) comprising said antibody or antigen-binding fragment thereof. The present invention also relates to modified immune cells expressing said CAR, or co-expressing said CAR and additional bioactive molecules (e.g. PD-1 antibody and/or mIL-15), and a method for preparing said modified immune cells. The present invention also relates to the use of such antibodies, CARs, and immune cells for the prevention and/or treatment of diseases associated with the expression of mesothelin, such as malignant pleural mesothelioma, pancreatic cancer, lung cancer, breast cancer, and ovarian cancer, and a method for the prevention and/or treatment of diseases associated with the expression of mesothelin, such as malignant pleural mesothelioma, pancreatic cancer, lung cancer, breast cancer, ovarian cancer, and other MSLN-positive tumors.

This document relates to engineered immune cells comprising a FAP-CAR and a tumor-CAR with differential expressions, their use in the treatment of tumors expressing FAP, as well as methods and materials for the preparation thereof.