This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize EGFR neoantigens comprising L858R mutations and restricted to HLA class I A11 allotype. Accordingly, aspects of the disclosure relate to a polypeptide comprising an antigen binding variable region comprising the amino acid sequence of a CDR3 of the disclosure or an amino acid sequence with at least 80% sequence identity to a CDR3 of the disclosure. Further aspects relate to an engineered T-cell Receptor (TCR) comprising a TCR-b polypeptide and a TCR-a polypeptide, wherein the TCR-b polypeptide comprises an amino acid sequence of a CDR3 of the disclosure or an amino acid sequence with at least 80% sequence identity to a CDR3 of the disclosure and the TCR-a polypeptide comprises the amino acid sequence of a CDR3 of the disclosure or an amino acid sequence with at least 80% sequence identity to a CDR3 of the disclosure.

In various embodiments, the present disclosure provides chimeric antigen receptors (CARs) which bind to mesothelin. The mesothelin CARs comprise an extracellular region comprising a binding domain that specifically binds to at least a portion of mesothelin, a transmembrane region, and an intracellular region comprising an effector domain or a portion or variant thereof and a costimulatory domain or a portion or variant thereof. Recombinant host cells expressing the mesothelin CARs are also provided, as well as compositions and methods of treatment, prevention, and manufacture comprising the same.

T cells comprising a molecule comprising (i) a target-specific antigen-binding domain, (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided.

The present invention relates to a novel T-cell receptor binding to MR1, and a use thereof. Unlike a conventional customized anticancer immune T cell therapeutic agent, which are limitedly used depending on cancer type and the expression of cancer antigens according to human leukocyte antigen (HLA) type, T cells in which a T-cell receptor is expressed can be applied to all types of cancer regardless of HLA type.

The present disclosure provides methods of anchoring active molecules on the surface of a cell, methods of anchoring at least two active molecules on the surface of a cell, and methods of enhancing an immune response to a target cell in a human.

Provided are a preparation method and an application of CD7-CAR-T cells. The method comprises: (i) providing a sample to be processed containing T cells, (ii) sorting and activating the T cells contained in the sample, so as to obtain activated T cells, (iii) introducing a first viral vector for expressing a CD7 blocking molecule into the activated T cells, so as to obtain CD7 blocked T cells, and (iv) introducing a second viral vector for expressing a CD7-CAR into the CD7-blocked T cells to obtain CD7-CAR-T cells. By adjusting the transfection sequence and transfection time of the lentivirus expressing the CD7 blocking molecule and the lentivirus expressing the CD7-CAR, transfection efficiency is improved, and the cytotoxicity of the CAR-T cells is enhanced.

The compositions and methods described herein are directed to treating solid tumor using CAR T therapy. For example, the compositions include CAR T cells comprising an extracellular domain that binds FCR1, MSLN, GPC-3, ALPP, CD70, CLDN6, ROR1, CD205, ACPP, ADAM12, or CLDN18.2.

N(57) Abstract: There is a need for new and alternative options for immune therapy of proliferative diseases such as cancer. This need C\11 may be address by providing a chimeric antigen receptor having an extracellular domain including a binding domain which recognises Nthe cancer-stem-cell-associated protein Lgr5; a transmembrane domain; and an intracellular signalling domain that activates a cellular .,, function. Such CAR T cells can be used to kill cancer cells and treat or prevent cancer in a subject.

The present invention relates to an engineered immune cell which comprises: (i) a target binding polypeptide comprising a target-binding domain and a first protein interaction domain, and (ii) a localising polypeptide comprising a second protein interaction domain, which binds to the first protein binding domain, and an intracellular retention signal. When the target binding polypeptide binds its target protein and also the localising polypeptide, expression of the target protein at the cell surface is reduced or eliminated because the target protein is retained in an intracellular compartment.

The present disclosure provides a chimeric antigen receptor (CAR) specific for albumin. The present disclosure also provides compositions comprising the CAR, polynucleotides encoding the CAR, vectors comprising a polynucleotide encoding the CAR, engineered cells comprising the CAR, and method using the same.