The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD28, and methods of use thereof.

The present invention relates to a method of screening for a cancer therapeutic agent using Cyclin B1, Cyclin-dependent kinase 1 (CDK1), and retinoic acid receptor responder 1 (RARRES1), and a composition for diagnosing cancer or predicting a prognosis using the same. As a result of having conducted intensive studies to discover molecular mechanisms for diagnosing cancer and predicting a prognosis, the inventors of the present invention confirmed that in cancer-derived samples, according to the degree of mutual binding between RARRES1 and CDK1 or Cyclin B1, the mitosis of cancer cells was arrested, the formation of CDK1-Cyclin B1 complexes was suppressed, and the degradation of these proteins was promoted, and thus RARRES1 was a crucial factor in the diagnosis of cancer, prognosis prediction, and the treatment of cancer. In addition, through these findings, it is anticipated that RARRES1 may be widely used in screening for a cancer therapeutic agent exhibiting a decrease in the degree of binding between CDK1 and Cyclin B1, an increase in the degree of binding between the RARRES1 gene and CDK1 or Cyclin B1, and a decrease in an amount or activity of the CDK1 protein or the Cyclin B1 protein, and in the development of drugs. In addition, the present invention relates to a targeting vector including a portion of the Rarres1 gene and sequences used in producing a conditional knockout animal model, an animal cell for producing a tumorigenic animal model, which is produced using the targeting vector, a tumorigenic Rarres1.sup.−/− animal model produced using the animal cell, a method of producing the animal model, and a method of screening for a cancer therapeutic agent by using the method. Thus, as a result of having conducted intensive studies to discover molecular mechanisms for diagnosing cancer and predicting a prognosis, the inventors of the present invention confirmed that a Rarres1.sup.−/− animal model was prone to spontaneous tumors and exhibited increased phosphorylation of CDK1 and Cyclin B1 and a high activity of a CDK1-Cyclin B1 complex, and thus it was confirmed that the tumor cell cycle progression was unusually rapid due to a decrease in protein degradation ability. In particular, it was confirmed that stem cell proliferation was increased, and chromosomes were unstable upon induction of mitotic defects and mitosis, from which it was confirmed that RARRES1 is a crucial factor in diagnosing cancer, predicting a prognosis, and treating cancer. Moreover, it is anticipated that the Rarres1.sup.−/− animal model can be variously used for screening for a cancer therapeutic agent and developing a drug, through the relationship between RARRES1

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric TIGIT (e.g., humanized TIGIT), and methods of use thereof.

Chimeric transmembrane immunoreceptors (CAR) targeted to PSCA are described.

A nucleic acid molecule can code for an Orf virus vector promoter. A recombinant Orf virus vector can be included in a cell. The nucleic acid molecule, the vector and/or the cell can be included in a composition. The recombinant Orf virus vector can be used for the production of a foreign gene.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric OX40, and methods of use thereof.

The present disclosure provides compositions and methods related to the generation and use of transgenic animal models having stem cell reporter systems. In particular, the present disclosure provides a novel transgenic animal model that expresses a nuclear-localized fluorescent reporter in cells endogenously expressing a leucine-rich repeat-containing G-protein coupled receptor (LGR) gene (e.g., LGR5gene). Given the role of LGR genes in stem cell and cancer biology, the transgenic animal models provided herein are useful for a wide range of therapeutic and diagnostic purposes.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD137, and methods of use thereof.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL15, and methods of use thereof.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD137, and methods of use thereof.