The present invention provides a non-human animal having human interleukin-34 (IL-34) in the body thereof; a method for producing a non-human animal having human microglia, which includes transplanting human CD34-positive hematopoietic stem cells into the non-human animal having human IL-34 in the body; and a method for producing human microglia, which includes obtaining human microglia from the non-human animal having human microglia.

The present invention relates to an isolated transgenic pig beta cell wherein the PKC and the PKA pathway are constitutively activated; to a transgenic pig islet comprising said transgenic pig beta cell; and to a transgenic pig comprising said transgenic pig beta cell or said transgenic pig islet. Another object of the invention is a device comprising a transgenic pig beta cell or a transgenic pig islet of the invention. The present invention also relates to the use of said transgenic pig beta cell, said transgenic pig islet, or said device for treating a disease, disorder or condition related to the impaired function of endocrine pancreas or of beta cell.

The present invention relates to an avian model enabling the amplification of human or animal circulating tumour cells (CTC) and to the use thereof for monitoring and determining the sensitivity of a patient or an animal suffering from cancer to one or more therapeutic agent(s), as well as for screening novel therapeutic agents intended for the treatment of cancer.

A method of inducing lymphangiogenesis in the brain or central nervous system of a subject is provided in which an effective amount of a lymphangiogenesis inducer is administered. A method of inducing lymphangiogenesis in a tumor in the brain or central nervous system of a subject is provided in which an effective amount of a lymphangiogenesis inducer is administered. A method of treating a cancer of the brain or central nervous system is also provided in which an effective amount of a lymphangiogenesis inducer is administered. An example of a lymphangiogenesis inducer is VEGFC. The lymphangiogenesis inducer can be in the form of a protein or a polynucleotide encoding the protein, such as an mRNA or AAV. The lymphangiogenesis inducer can be administered to the cistemamagna or directly into the lymphatic system. An immunotherapeutic agent, such as a checkpoint inhibitor, may also be administered.

A method of producing a vaccine for a cancer and/or tumor and stage of interest is disclosed. The method includes identifying a first population of peptides that are immunoreactive with a set of biological samples obtained from a set of test subjects that have been identified as having the cancer and/or tumor of interest, and preparing a cancer vaccine composition for the cancer of interest, wherein the cancer vaccine composition comprises a second population of peptides comprising one or more peptides in the first population or a nucleic acid sequence encoding the one or more peptides, thereby producing the vaccine for the cancer and/or tumor of interest. Also disclosed are vaccine compositions and methods of use thereof.

Provided is a method for developing a secondary organ by using a non-human animal in which organ formation is inhibited, for the purpose of establishing a process for producing a functional cell such as a β cell within the body of an animal such as a pig, the method including the step of raising a newborn or a fetus of the non-human animal in which organ formation is inhibited by complementing at least a part of the function of the organ whose formation is inhibited.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.

Disclosed is a bispecific antibody that specifically binds to surface antigens CD3 of immune cells and CD20 antigens on the surfaces of tumor cells, and that can bind to human CD3 with high affinity, inducing T cell proliferation, and mediating tumor cell killing. The bispecific antibody in an in vitro test was able to mediate the specific killing of target cells by T cells. The construction method thereof is simple, avoiding the possibility of mismatch between two sets of light chains and heavy chains of heterobispecific antibodies, thereby reducing the difficulty of antibody purification. The affinity of the obtained antibody is high, the side effects caused by cytokines are small, and safety is high.

The present invention provides: a composition for reconstituting human skin tissue having hair follicles, the composition characterized by containing human epidermal cells and human dermal cells, the human dermal cells containing cell groups of human hair papilla derived from non-embryos via spheroid formation; and a human skin tissue model animal to which said composition is applied. The invention also provides a method for producing said composition and animal.