Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a genetically modified Th17 cell to express a CAR having an antigen binding domain, a transmembrane domain, and an ICOS intracellular signaling domain.

Abstract: The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).

Abstract: Disclosed herein are anti-mesothelin antibodies and antigen-binding fragments, chimeric antigen receptors (“CARs”) having these anti-mesothelin antibodies and antigen-binding fragments (“mesothelin CARs”) and genetically modified immune effector cells having such mesothelin CARs. Polynucleotides encoding the anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. Compositions comprising anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. The present disclosure also relates to uses of the anti-mesothelin antibodies and antigen-binding fragments and genetically modified immune effector cells having such mesothelin CARs in cancer treatment.

Abstract: The present disclosure provides modified immune cells or precursors thereof (e.g. T cells) comprising a chimeric antigen receptor (CAR) capable of binding human PSCA. CARs capable of binding human PSCA, and nucleic acids encoding the same are also provided. Provided herein are bispecific CARs capable of binding human PSCA and human PSMA, nucleic acids encoding the same, and modified immune cells comprising the same. Modified immune cells comprising a PSMA CAR and a PSCA CAR are also provided. Compositions and methods of treatment are also provided.

Abstract: The present disclosure provides modified immune cell (e.g., modified T cell) comprising an exogenous T cell receptor (TCR) having specificity for NY-ESO-1. The present disclosure provides modified immune cells or precursors thereof (e.g., modified T cells) comprising an exogenous TCR and a switch receptor. Gene edited modified cells are also provided, such that the expression of one or more of an endogenous T-cell receptor gene (e.g., TRAC, TRBC) or an endogenous immune checkpoint gene (e.g. PD-1 or TIM-3) is downregulated.

Abstract: The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an chimeric antigen receptor and bispecific antibodies in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. Certain aspects include modified T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

Abstract: The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an intracellular signaling molecule in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a T cell, genetically modified to express a chimeric antigen receptor (CAR), a bispecific antibody, or a combination thereof to a subject. The CAR and bispecific antibody of the invention can comprise a human antibody, a humanized antibody, or antigen-binding fragments thereof.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a T cell, genetically modified to express a chimeric antigen receptor (CAR), a bispecific antibody, or a combination thereof to a subject. The CAR and bispecific antibody of the invention can comprise a human antibody, a humanized antibody, or antigen-binding fragments thereof.

Abstract: The present application relates to an antigen-binding protein and use thereof, wherein the antigen-binding protein comprises a VH and a VL, wherein the VH comprises an HCDR1, an HCDR2 and an HCDR3, wherein the HCDR1 comprises an amino acid sequence as set forth in SEQ ID NO: 10, the HCDR2 comprises an amino acid sequence as set forth in SEQ ID NO: 12, the HCDR3 comprises an amino acid sequence as set forth in SEQ ID NO: 14; and the VL comprises an LCDR1, an LCDR2 and an LCDR3, wherein the LCDR1 comprises an amino acid sequence as set forth in SEQ ID NO: 2, the LCDR2 comprises an amino acid sequence as set forth in SEQ ID NO: 4, and the LCDR3 comprises an amino acid sequence as set forth in SEQ ID NO: 6. The present application also relates to a pharmaceutical composition comprising the antigen-binding protein and use thereof for the treatment of a cancer.

Abstract: The present disclosure provides modified immune cells or precursors thereof (e.g. T cells) comprising a chimeric antigen receptor (CAR) capable of binding human PSCA. CARs capable of binding human PSCA, and nucleic acids encoding the same are also provided. Provided herein are bispecific CARs capable of binding human PSCA and human PSMA, nucleic acids encoding the same, and modified immune cells comprising the same. Modified immune cells comprising a PSMA CAR and a PSCA CAR are also provided. Compositions and methods of treatment are also provided.

Abstract: The present disclosure provides modified immune cell (e.g., modified T cell) comprising an exogenous T cell receptor (TCR) having specificity for NY-ESO-1. The present disclosure provides modified immune cells or precursors thereof (e.g., modified T cells) comprising an exogenous TCR and a switch receptor. Gene edited modified cells are also provided, such that the expression of one or more of an endogenous T-cell receptor gene (e.g., TRAC, TRBC) or an endogenous immune checkpoint gene (e.g., PD-1 or TIM-3) is downregulated.

Abstract: Disclosed herein are anti-mesothelin antibodies and antigen-binding fragments, chimeric antigen receptors (“CARs”) having these anti-mesothelin antibodies and antigen-binding fragments (“mesothelin CARs”) and genetically modified immune effector cells having such mesothelin CARs. Polynucleotides encoding the anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. Compositions comprising anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. The present disclosure also relates to uses of the anti-mesothelin antibodies and antigen-binding fragments and genetically modified immune effector cells having such mesothelin CARs in cancer treatment.

Abstract: Disclosed herein are fusion proteins having a first domain that activates an antigen-presenting cell (APC) (e.g., a dendritic cell) by binding to an activation receptor of the APC, and a second domain that activates an immune effector cell (e.g., a T cell) by targeting a co-stimulatory signaling pathway of the immune effector cell, as well as polynucleotides that encode such fusion proteins. Disclosed herein are also genetically engineered immune effector cells expressing such fusion protein, methods of their production, and their uses in treatment of diseases such as cancers.

Abstract: Disclosed herein are anti-BCMA antibodies and antigen-binding fragments, chimeric antigen receptors (“CARs”) having these anti-BCMA antibodies and antigen-binding fragments (“BCMA CARs”) and genetically modified immune effector cells having such BCMA CARs. Polynucleotides encoding the anti-BCMA antibodies and antigen-binding fragments and BCMA CARs are also provided herein. Compositions comprising anti-BCMA antibodies and antigen-binding fragments and BCMA CARs are also provided herein. The present disclosure also relates to use of the anti-BCMA antibodies and antigen-binding fragments and genetically modified immune effector cells having such BCMA CARs in cancer treatment.

Abstract: The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an intracellular signaling molecule in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

Abstract: The present invention includes a method for expanding a population of electroporated T cells. The method includes electroporating a population of cells comprising T cells with mRNA encoding a chimeric membrane protein comprising an antigen binding domain to a molecule and an intracellular domain of a co-stimulatory molecule, wherein the cultured T cells expand at least 10 fold. The invention further includes an expanded population of T cells, compositions comprising the cells and methods of treatment.

Abstract: Disclosed herein are fusion proteins having a first domain that activates an antigen-presenting cell (APC) (e.g., a dendritic cell) by binding to an activation receptor of the APC, and a second domain that activates an immune effector cell (e.g., a T cell) by targeting a co-stimulatory signaling pathway of the immune effector cell, as well as polynucleotides that encode such fusion proteins. Disclosed herein are also genetically engineered immune effector cells expressing such fusion protein, methods of their production, and their uses in treatment of diseases such as cancers.

Abstract: The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).

Abstract: The present disclosure provides modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in an endogenous gene locus encoding DNMT3A. Compositions and methods of treatment are also provided.