Abstract: Provided are binding molecules, such as TCRs or antigen binding fragments thereof and antibodies and antigen-binding fragments thereof, such as those that recognize or bind human papilloma virus (HPV) 16, including HPV 16 E6 and HPV 16 E7. Also provided are engineered cells containing such binding molecules, compositions containing the binding molecules or engineered cells, and methods of treatment, such as administration of the binding molecules, engineered cells, or compositions.

Abstract: The preset disclosure provides chimeric activation receptors comprising (i) a TGF?-binding domain and (ii) a CD2 costimulatory domain. In some aspects, the TGF?-binding domain comprises an extracellular domain of a TGF? receptor. Other aspects of the disclosure are directed to nucleic acid molecules encoding a chimeric activation receptor, cells comprising the chimeric activation receptor and/or a nucleic acid molecule encoding the same, and methods of use thereof in the treatment of a disease or condition (e.g., a tumor) in a subject in need thereof.

Abstract: Provided herein are BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof such as heavy chain variable (VH) regions and single-chain antibody fragments, and chimeric receptors comprising the anti-BCMA binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-BCMA antibodies or antigen-binding fragments thereof specifically bind to BCMA-1. Among the anti-BCMA antibodies are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs or BCMA-binding molecules and uses thereof such as in adoptive cell therapy.

Abstract: Provided herein are BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof such as heavy chain variable (VH) regions and single-chain antibody fragments, and chimeric receptors comprising the anti-BCMA binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-BCMA antibodies or antigen-binding fragments thereof specifically bind to BCMA-1. Among the anti-BCMA antibodies are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs or BCMA-binding molecules and uses thereof such as in adoptive cell therapy.

Abstract: CRISPR/CAS-related genome editing systems, compositions and methods for targeting the TGFBR2 locus, as well as cells edited using these systems, compositions and methods are provided.

Abstract: Provided herein are engineered immune cells, e.g. T cells, expressing a recombinant receptor, that contain a modified transforming growth factor-beta receptor type-2 (TGFBR2) locus encoding the recombinant receptor or a portion thereof. In some aspects, the cells are engineered by targeted integration of a transgene sequence encoding the recombinant receptor or a portion thereof, at a TGFBR2 genomic locus. Also provided are cell compositions containing the engineered immune cells, nucleic acids for engineering cells, and methods, kits and articles of manufacture for producing the engineered cells, such as by targeting a transgene sequence encoding a recombinant receptor or a portion thereof for integration into a region of a TGFBR2 genomic locus. In some embodiments, the engineered cells, e.g. T cells, can be used in connection with cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered cells.

Abstract: Provided are chimeric antigen receptors (CARs), which contain antibody portions specific to G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) and polynucleotides that encode CARs specific for GPRC5D. The disclosure further relates to genetically engineered cells, containing such GPRCSD-binding receptors, and uses thereof in adoptive cell therapy.

Abstract: Provided herein are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain plasma cell malignancy. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) specific to B-cell maturation antigen (BCMA). In some embodiments, the methods are for treating subjects with multiple myeloma (MM). Also provided are genetically engineered cells containing such BCMA-binding receptors for uses in adoptive cell therapy.

Abstract: Provided herein are chimeric receptors, such as chimeric antigen receptors (CARs), comprising BCMA-binding molecules, such as anti-BCMA antibodies and antigen-binding fragments thereof, such as heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof such as in adoptive cell therapy.

Abstract: Provided are binding molecules, such as TCRs or antigen binding fragments thereof and antibodies and antigen-binding fragments thereof, such as those that recognize or bind human papilloma virus (HPV) 16, including HPV 16 E6 and HPV 16 E7. Also provided are engineered cells containing such binding molecules, compositions containing the binding molecules or engineered cells, and methods of treatment, such as administration of the binding molecules, engineered cells, or compositions.

Abstract: Provided herein are chimeric receptors, such as chimeric antigen receptors (CARs), comprising BCMA-binding molecules, such as anti-BCMA antibodies and antigen-binding fragments thereof, such as heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof such as in adoptive cell therapy.

Abstract: Provided herein are methods for engineering immune cells, cell compositions containing engineered immune cells, kits and articles of manufacture for targeting nucleic acid sequence encoding a portion of a recombinant receptor, e.g., a recombinant T cell receptor (TCR), to a particular genomic locus and/or for modulating expression of the gene at the genomic locus, and applications thereof in connection with cancer immunotherapy, such as adoptive transfer of engineered T cells. In some aspects, the nucleic acid sequence integrates in-frame into the locus of a receptor encoding gene, and in some aspects, results in expression of the whole recombinant receptor.

Abstract: Provided are methods for engineering immune cells, cell compositions containing engineered immune cells, kits and articles of manufacture for targeting nucleic acid sequence encoding a recombinant receptor to a particular genomic locus and/or for modulating expression of the gene at the genomic locus, and applications thereof in connection with cancer immunotherapy comprising adoptive transfer of engineered T cells. These may involve genetic disruption of at least one site within a TRAC gene and/or a TRBC gene and integration of the transgene encoding for the recombinant receptor at or near one of the at least one target site.

Abstract: Provided herein are BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof such as heavy chain variable (VH) regions and single-chain antibody fragments, and chimeric receptors comprising the anti-BCMA binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-BCMA antibodies or antigen-binding fragments thereof specifically bind to BCMA-1. Among the anti-BCMA antibodies are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs or BCMA-binding molecules and uses thereof such as in adoptive cell therapy.

Abstract: Provided herein are chimeric receptors, such as chimeric antigen receptors (CARs), comprising BCMA-binding molecules, such as anti-BCMA antibodies and antigen-binding fragments thereof, such as heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof such as in adoptive cell therapy.