Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.

Provided are methods of generating chimeric antigen receptors (CAR). In some embodiments, library screening of CAR is performed by generating a vector encoding the CAR from random attachment of vectors from libraries of vectors encoding antigen-binding domains (e.g., scFv regions), hinge regions, and endodomains. In some embodiments, the vectors contain a transposon.

The present invention provides methods of use for compositions comprising an immunotherapeutic such as chimeric antigen receptor T cells (CAR-T cells), and specifically those that target a tumor antigen cleaved by gamma secretase, in combination with bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (I) or prodrugs thereof;

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for treating lymphomas.

A multiple myeloma-specific CAR+ T-cell composition and a vaccine composition composed of 3 cells lines, the U266, H929, and K562 are described. Methods are described for using the vaccine composition in conjunction with the MM-specific CAR+ T cell composition in methods of immunizing against plasma cell disorders, including multiple myeloma and related disorders.

Provided herein are nucleic acids, expression cassettes, modified lymphocytes and compositions comprising the same which include a sequence encoding a gene of Table 1. In some embodiments, the gene is LTBR. In certain embodiments, the cell is a T cell. In certain embodiments, the cell further comprises a CAR or engineered TCR. Methods of treatment using the provided compositions are also described.

Provided herein are multi-functional chimeric antigen receptor (CAR)-based compositions and their use in directing immune responses to target cells. The compositions have uses that include treating hyperproliferative disorders such as cancer. The provided methods generally include the use of a CAR cell in combination with an Adapter. The Adapter confers the ability to modulate, alter, and/or redirect CAR cell-mediated immune response in vitro and in vivo. In some embodiments, the CAR cell comprises a genetic modification to reduce or eliminate the expression of a targeted antigenic determinant.

The present disclosure provides compositions, including modified peripheral blood mononuclear cells (PBMCs) with reduced expression of Slc16a11 and/or reduced activity of MCT11. Also provided are siRNAs and gRNAs targeting Slc16a11. Methods of using the disclosed compositions in the treatment of cancer are also provided.

The disclosure provides antibody molecules that bind to TCR V? regions and multispecific molecules comprising said antibody molecules. Additionally, disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, pharmaceutical compositions comprising aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

Provided herein are T-cell receptor (TCR) fusion proteins (TFPs). T-cells engineered to express one or more TFPs. and methods of use thereof for the treatment of diseases, including cancer.

The present disclosure relates generally to the field of immunology, and particularly relates to hybrid chimeric antigen receptors designed to combine fast time-scale intracellular signal transduction and long time-scale transcription regulation. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions or diseases, such as cancers.