The present invention describes combination treatment comprising a PD-1 axis binding antagonist and an agent that decreases or inhibits TIGIT expression and/or activity and methods for use thereof, including methods of treating conditions where enhanced immunogenicity is desired such as increasing tumor immunogenicity for the treatment of cancer or chronic infection.

An atopic dermatitis model non-human animal, containing a gene mutation in which a complex containing dedicator of cytokinesis 8 (DOCK8) protein, mammalian STE20-like kinase 1 (MST1) protein, and endothelial PAS domain protein 1 (EPAS1) protein is not formed in CD4.sup.+ T cells.

The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdc.sup.scid IL2re.sup.tmlWjl/SzJ (NSG), NOD.Cg-Rag1.sup.tm1Mom Il2rg.sup.tmlWjl/SzJ (NRG) and NOD.Cg-Prkdc.sup.scid Il2rg.sup.tm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice. Methods for assessment of therapeutic antibodies or putative therapeutic antibodies in the genetically modified immunodeficient mice characterized by an intact complement system are provided according to specific aspects of the present invention.

Described herein are rats with a hepatic deficiency comprising decreased function, activity, or expression of an enzyme in the tyrosine catabolic pathway (such as fumarylacetoacetate hydrolase), and methods of using the same for in vivo engraftment and expansion of heterologous hepatocytes, such as human hepatocytes, analysis of human liver disease, and analysis of xenobiotics. Also disclosed is the use of immunodeficient rats for the engraftment and expansion of heterologous hepatocytes.

Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.

The present disclosure relates to genetically modified non-obese diabetic (NOD) mice deficient in murine class I MHC molecules, class II molecules, or both class I and class II MHC molecules. The MHC knockout transgenic mice provided herein are useful, for example, for developing therapies for diabetes.

The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

The present application, in some embodiments, is directed to a polynucleotide including: (a) a first nucleic acid molecule including a sequence of a human endogenous Bruton's tyrosine kinase (BTK) promoter; and (b) a second nucleic acid molecule including a codon optimized sequence encoding a BTK or a functional analog thereof. Further provided are an expression vector, a cell, and a composition, all of which include the polynucleotide of the invention, and a method of using same, such as for treating X-linked Agammaglobulinemia (XLA) in a subject in need thereof.

Provided are genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL33, and methods of use thereof.

The present disclosure provides for transgenic swine, comprising one or more nucleotide sequences encoding one or more HLA I polypeptides and/or one or more HLA II polypeptides inserted into one or more native SLA loci of the swine genome, methods of making and methods of using.

The present disclosure also provides for improved methods of making human immune system mice.