An object of the present invention is to provide an evaluation system capable of detecting an extracellular purinergic receptor ligand minimally invasively, chronologically and systemically, and the present invention provides a genetically modified non-human animal expressing a first fusion protein and a second fusion protein for detecting an extracellular purinergic receptor ligand, in which the first fusion protein comprises a membrane protein that binds to a purinergic receptor ligand, and a first reporter protein, and the second fusion protein comprises a protein that binds to the membrane protein bound to the ligand, and a second reporter protein; and a cell thereof.

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.

The present invention relates to a chimeric costimulatory antigen receptor (CoStAR) useful in adoptive cell therapy (ACT), and cells comprising the CoStAR. The CoStAR can act as a modulator of cellular activity enhancing responses to defined antigens. The present invention also provides CoStAR proteins, nucleic acids encoding the CoStAR and therapeutic uses thereof.

Compositions and methods comprising novel deaminase polypeptides for targeted editing of nucleic acids are provided. Compositions comprise deaminase polypeptides. Also provided are fusion proteins comprising a DNA-binding polypeptide and a deaminase of the invention. The fusion proteins include RNA-guided nucleases fused to deaminases, optionally in complex with guide RNAs. Compositions also include nucleic acid molecules encoding the deaminases or the fusion proteins. Vectors and host cells comprising the nucleic acid molecules encoding the deaminases or the fusion proteins are also provided.

The present invention is situated in the field of multimers used for targeted therapies. More particularly, the invention relates to methods for preparing multifunctional heteromultimeric protein complexes with a defined ratio of functional components and to multifunctional heteromultimeric protein complexes for directing complement-dependent cytolysis, optionally comprising a scaffold, which display three or more different functional components present in a defined relative ratio, of which one is a tracking component.

The present invention is situated in the field of multimers used for targeted therapies. More particularly, the invention relates to methods for preparing multifunctional heteromultimeric protein complexes with a defined ratio of functional components and to multifunctional heteromultimeric protein complexes for directing complement-dependent cytolysis, optionally comprising a scaffold, which display three or more different functional components present in a defined relative ratio, of which one is a tracking component.

The disclosure provides methods and compositions that are useful to lessen and/or cure bacterial biofilms and treat diseases or disorders associated with biofilms using one or more novel polypeptide vaccines, antibodies, antibody fragments and compositions. Bacteria that cannot form functional biofilms are more readily cleared by the remainder of the host's immune system and/or traditional antibiotics.

Disclosed herein is a novel chimeric antigen receptor and use thereof. The novel chimeric antigen receptor consists of a signal peptide, an antigen binding domain, a transmembrane region, and an intracellular signal domain, and comprises a 4-1BB signal peptide and/or a 4-1BB molecular transmembrane region. Nucleic acid sequences of various chimeric antigen receptors are separated and purified and provided is a chimeric antigen receptor and a CAR-T cell which are specific for a CD19 malignant tumor antigen. In the malignant tumor killing test of hematological cell lines, the ability of immune cells to target and recognize tumor cells is significantly enhanced, and the killing activity against tumor cells is also enhanced.

Disclosed herein is a novel chimeric antigen receptor and use thereof. The novel chimeric antigen receptor consists of a signal peptide, an antigen binding domain, a transmembrane region, and an intracellular signal domain, and comprises a 4-1BB signal peptide and/or a 4-1BB molecular transmembrane region. Nucleic acid sequences of various chimeric antigen receptors are separated and purified and provided is a chimeric antigen receptor and a CAR-T cell which are specific for a CD19 malignant tumor antigen. In the malignant tumor killing test of hematological cell lines, the ability of immune cells to target and recognize tumor cells is significantly enhanced, and the killing activity against tumor cells is also enhanced.

The invention concerns fusion proteins, wherein two endoglycosidases are fused, possibly via a linker. The fusion enzymes according to the invention have structure (1): EndoX-(L).sub.p-EndoY (1), wherein EndoX is an endoglycosidase, EndoY is an endoglycosidase distinct from EndoX, L is a linker and p is 0 or 1. Such fusion enzymes capable of trimming glycoproteins comprising at least two distinct glycoforms in a single step. The invention further concerns the use of the fusion enzyme according to the invention for trimming glycoproteins. In another aspect, the invention relates to the process of production of the fusion enzyme. In a further aspect, the inventions concerns a process for trimming glycoproteins, comprising trimming the glycoprotein with a fusion enzyme according to the invention, to obtain a trimmed glycoprotein.