Modified non-human mammalian hepatoma cell lines that express hepatitis C virus (HCV) antigens and which are capable of generating tumours in a syngeneic animal model are provided. The cell lines are generated by genomic integration of an expression construct that comprises one or more HCV antigen-encoding sequences under the control of a constitutive promoter. The expression construct further comprises a selectable marker and a reporter gene under the control of the same promoter. The cell lines are useful for testing prophylactic and therapeutic vaccines against HCV either in vitro or in vivo.

The invention described herein provides non-HLA matched humanized mouse model (e.g., NSG mouse model) with patient-derived xenograft (PDX), as well as methods of making and using the same.

Disease model pigs produced by nuclear transplantation, disease model pigs exhibiting stable phenotypes and production methods thereof are provided. Chimeric pigs for producing disease model pigs exhibiting stable phenotypes, genital glands thereof, and germ cells thereof are also provided. A method for producing a genetically modified disease model pig, includes: (a) transplanting a nucleus of a genetically modified cell into cytoplasm of an egg; (b) developing an obtained clonal embryo in a womb of a female pig to obtain an offspring; and mating the obtained offspring or having the offspring undergo sexual reproduction to further obtain the genetically modified offspring as a disease model pig.

Provided is a method for producing an animal model of osteoblastic bone metastasis. A non-human animal in which an osteoblastic lesion is formed in a wide range has been successfully produced with a probability of 100% by: administering a calcineurin inhibitor to a non-human animal; and injecting a tumor cell into an artery or a vein of the non-human animal, wherein the non-human animal and the tumor cell are in an allogeneic or xenogeneic relation.

The presently disclosed subject matter provides hydrogel precursor compositions (e.g., solutions) for forming three-dimensional hydrogels that support growth of physiologically relevant tissue when at least one cell is cultured in the three-dimensional hydrogel, kits comprising the hydrogel precursor composition, three-dimensional hydrogels, methods of forming the three-dimensional hydrogels, methods of growing the physiologically relevant tissue using the three-dimensional hydrogels, physiologically relevant tissue grown in the three-dimensional hydrogels, methods of producing hormone-responsive tissue (e.g., milk-producing mammary tissue and related methods of producing milk), methods of screening for candidate agents useful for modulating hormonal responses (e.g., modulating milk production), method of screening for candidate therapeutic agents using the physiologically relevant tissue grown in the three-dimensional hydrogels (e.g., personalized cancer treatments), and related methods of treatment (e.g., administering agents identified using the methods herein, transplanting physiologically relevant tissue produced using the methods, etc.).

Animal models that are permissive for human polyomaviruses and their uses for the screening of candidate agents are described.

Provided herein is a model, in particular a mouse model, for assessing or evaluating toxicity to an immunotherapy, for example a therapeutic cell therapy, such as a cell therapy containing engineered cells, such as T cells, expressing a recombinant receptor, e.g. a chimeric antigen receptor (CAR). Also provided is a method for generating the mouse model. Also provided herein are methods of use for the mouse models of toxicity, such as to evaluate modified or alternative immunotherapies, and/or to evaluate test agents, including agents to assess as potential interventions to reduce, prevent, or ameliorate toxicity to immunotherapy in human subjects and/or for use in combination with an immunotherapy, e.g. CAR−T cell therapy.

The present disclosure provides pharmaceutical compositions comprising CD80 extracellular domain (ECD)-fragment crystallizable (Fc) fusion molecules. The present disclosure also provides methods for treating solid tumors by administering such pharmaceutical compositions.

There is disclosed patient derived xenograft (PDXs) cells/systems/models and/or derivatives, parental (unlabelled) and/or labelled, expressing a fluorescent protein or a luciferase, or a combination thereof; for evaluating therapies comprising nasopharyngeal carcinoma (EBV positive and/or EBV negative). In another embodiment, there is disclosed a method of evaluating the efficacy of an agent used to treat nasopharyngeal carcinoma (NPC) comprising: preparing a non-human model; whereby the non-human model carries cells from NPC xenograft; labelling the cells from the NPC xenograft with gfp-luc2 marker using a lentiviral vector system; and growing the cells in short term in vitro culture; including adaptation of said culture into multi-well plates for use in further screening and/or evaluation assays; wherein the NPC xenograft is PDX.

The invention involves a method for modulating leukocyte activity, comprising delivering to a leukocyte a vector containing nucleic acid molecule(s), whereby the leukocyte contains Cas9 and the vector expresses one or more RNAs to guide the Cas9 to introduce mutations in one or more target genetic loci in the leukocyte, thereby modulating expression of one or more genes expressed in the leukocyte. The invention also involves identifying genes associated with leukocyte responses and experimental modeling of aberrant leukocyte activation and diseases associated with leukocytes by introducing mutations into leukocytes. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate leukocyte associated diseases.