The present application provides antibody-TCR chimeric constructs comprising an antibody moiety that specifically binds to a target antigen fused to a TCRM capable of recruiting at least one TCR-associated signaling module. Also provided are methods of making and using these constructs.

Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)- chain and a heterologous TCR- chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Provided herein are methods and compositions for modifying an endogenous cell surface protein in a human cell by inserting a heterologous nucleic acid sequence in a target region of a nucleic acid encoding the endogenous cell surface protein.

The present application relates to PD-1 switch receptors, e.g., chimeric PD-1 switch receptors, in combination with a FAS dominant negative receptor, optionally in combination with a safety switch, e.g., truncated EGFR, which can be used in adoptive cell therapy to treat human diseases and disorders.

The application provides genetically modified cell receptors (TCRs) specific for an epitope from cancer antigen NY-ESO-1. Also provided are related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells, including but not limited to genetically engineered cells, and pharmaceutical compositions. The application further provides the use of such modified T cell receptors (TCRs) and related compositions for cancer immunotherapy (e.g., adoptive cell therapy).

Provided herein are genetically modified T cells that exhibit increased proliferation compared to wild-type T cells when stimulated, methods of generating such T cells, and methods of using the T cells for the treatment of a disease such as cancer.

The present invention provides isolated T cell receptors (TCRs) that specifically bind to an HLA-displayed New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) peptides, as well as therapeutic and diagnostic methods of using those isolated TCRs.

The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for a) melanoma antigen family A (MAGE A)-3 in the context of HLA-A1 or b) MAGE-A12 in the context of HLA-Cw7. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are further provided by the invention.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

The present disclosure is directed recombinant T cell receptors capable of binding an NY-ESO-1 epitope and nucleic acid molecules encoding the same. In some embodiments, the nucleic acid molecules further comprise a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR. Other aspects of the disclosure are directed to vectors comprising the nucleic acid molecule and cells comprising the recombinant TCR, the nucleic acid molecule, or the vector. Still other aspects of the disclosure are directed to methods of using the same. In some embodiments, the methods comprise treating a cancer in a subject in need thereof.