Abstract: The invention provides methods of making immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions generated by such methods.

Abstract: Sortase molecules and methods described herein allow for the construction of a CAR or CAR member, e.g., in situ, on a CARX, e.g., CART, cell. For example, sortase mediated transfer of an antigen binding domain, e.g., a scFv, onto a CAR member having a sortase acceptor motif in place of an antigen binding domain can provide for a complete CAR member on a cell wherein the cell does not comprise nucleic acid that encodes the complete CAR member.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Abstract: The present invention features the use of chimeric CD3 proteins to modulate T cell Receptor (TCR) signaling. Specifically, the invention is based, in part, on the discovery that multiple chimeric CD3 proteins (e.g., CD3delta, CD3gamma, and CD3 epsilon) having all or most of their extracellular domain fused to more than one antigen binding domain can activate the TCR in the presence of one or more cognate antigens. The invention is further based on the observation that the above chimeric proteins can be potentiated through the inclusion of a co-stimulatory domain in the intracellular portion of the chimeric molecule. Thus, the preferred elements of the engineered signaling complexes of the invention include more than one antigen binding domain, an extracellular domain derived from one of the above CD3 proteins, and an intracellular co-stimulatory domain.

Abstract: The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1): X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13??I or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor.

Abstract: This application provides mutant sortase molecules and methods of making and using them. In a first aspect, disclosed herein, are sortase molecules having one or a combination of mutations. In an embodiment, a sortase molecule is optimized for a parameter of enzyme performance, e.g., Ca++ dependency (or independency) or reaction rate.

Abstract: Sortase molecules and methods described herein allow for the construction of a CAR or CAR member, e.g., in situ, on a CARX, e.g., CART, cell. For example, sortase mediated transfer of an antigen binding domain, e.g., a scFv, onto a CAR member having a sortase acceptor motif in place of an antigen binding domain can provide for a complete CAR member on a cell wherein the cell does not comprise nucleic acid that encodes the complete CAR member.

Abstract: The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1): X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13??I or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor.

Abstract: The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I? (SEQ ID NO: 1): or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor.

Abstract: The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1): X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13??I or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor.

Abstract: The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I? (SEQ ID NO: 1): or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor.

Abstract: The present invention relates to methods for ligation. The invention provides novel reagents and methods for ligating an acyl donor compound with an acyl acceptor compound. Provided acyl donor compounds comprise a transamidase recognition sequence that allows ligation with a nucleophilic acyl acceptor in the presence of transamidase. The invention further provides kits comprising acyl donor compounds and optionally comprising other reagents for ligation.

Abstract: The present invention, in some aspects, provides methods, reagents, and kits for the functionalization of proteins on the surface of viral particles, for example, of bacteriophages, using sortase-mediated transpeptidation reactions. Some aspects of this invention provide methods for the conjugation of an agent, for example, a detectable label, a binding agent, a click-chemistry handle, or a small molecule to a surface protein of a viral particle. Kits comprising reagents useful for the generation of functionalized viral particles are also provided, as are precursor proteins that comprise a sortase recognition motif, and viral particles comprising such precursor proteins. Nucleic acids encoding viral proteins comprising a sortase recognition motif and expression vectors comprising such nucleic acids are also provided.

Abstract: The present invention provides modified multi-chain and multi-subunit proteins and methods for making them. In some protease embodiments the proteins are modified AB5 toxins in which a compound of interest is attached to the A1 chain.

Abstract: The present invention relates to methods for ligation. The invention provides novel reagents and methods for ligating an acyl donor compound with an acyl acceptor compound. Provided acyl donor compounds comprise a transamidase recognition sequence that allows ligation with a nucleophilic acyl acceptor in the presence of transamidase. The invention further provides kits comprising acyl donor compounds and optionally comprising other reagents for ligation.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.