The present invention relates to methods for developing engineered immune cells such as T-cells for immunotherapy that have a higher potential of persistence and/or engraftment in host organism. IN particular, this method involves an inactivation of at least one gene involved in self/non self recognition, combined with a step of contact with at least one non-endogenous immunosuppressive polypeptide. The invention allows the possibility for a standard and affordable adoptive immunotherapy, whereby the risk of GvH is reduced.

A catalyst support comprising at least 95% silicon carbide, having surface areas of ≤10 m.sup.2/g and pore volumes of ≤1 cc/g. A method of producing a catalyst support, the method including mixing SiC particles of 0.1-20 microns, SiO.sub.2 and carbonaceous materials to form an extrusion, under inert atmospheres, heating the extrusion at temperatures of greater than 1400° C., and removing residual carbon from the heated support under temperatures below 1000° C. A catalyst on a carrier, comprising a carrier support having at least about 95% SiC, with a silver solution impregnated thereon comprising silver oxide, ethylenediamine, oxalic acid, monoethanolamine and cesium hydroxide. A process for oxidation reactions (e.g., for the production of ethylene oxide, or oxidation reactions using propane or methane), or for endothermic reactions (e.g., dehydrogenation of paraffins, of ethyl benzene, or cracking and hydrocracking hydrocarbons).

The present invention relates to the use of an embryonated egg model grafted with tumour cells to investigate anti-cancer effectiveness or to screen immunotherapeutic molecules, in the absence of immune effector cells other than those in the grafted egg.

A NOD.Cg-Prkdc.sup.scidH2rg.sup.tm1 Wjl/SzJ.(NOD-scid-IL2rγ.sup.null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-Prkdc.sup.scidH2-K1.sup.tml Bpe H2-Ab1.sup.eml Mvw H2-D1.sup.tml Bpe H2rg.sup.tm Wjl/SzJ (NSG-K.sup.b D.sup.b).sup.null(IA.sup.null)) mouse, NSG-RIP-DTR (K.sup.b D.sup.b).sup.null(IA.sup.null) mouse, or a NOD.Cg-B2m.sup.tmlUnePrKdc.sup.scidH2.sup.dlAb1-E.sup.αH2rg.sup.tm1 Wjl/SzJ (NSG-B2M.sup.null(IA IE.sup.null)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

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 in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.

This invention provides a therapeutic method for treatment of EGFR gene mutation-positive lung cancer using the REIC/Dkk-3 gene in combination with the EGFR tyrosine kinase inhibitor, the PD-1/-L1 immune checkpoint pathway inhibitor, and/or the molecular-targeted agent. This invention provides a therapeutic agent comprising, as an active ingredient, the REIC/Dkk-3 gene, which is used in combination with the EGFR tyrosine kinase inhibitor, the PD-1/-L1 immune checkpoint pathway inhibitor, and/or the molecular-targeted agent for treatment of EGFR gene mutation-positive lung cancer.

Genetically modified non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

The result of orally administering saliva derived from a Crohn’s disease patient or an ulcerative colitis patient to germ-free mice has revealed that Th1 cells markedly increased in the colons. Further, from the bacterial microbiota in the intestines of the mice in which such an increase in Th1 cells were observed, bacteria have been successfully isolated which caused strong Th1 cell induction in the colon upon intestinal colonization.

Disclosed is a novel means which makes it possible to steadily mass-produce knockout individuals even in large animals. The method of the present invention is a method for producing a non-human large mammal or fish (non-human animal) that produces gametes originating in a different individual, and comprises transplanting at least one pluripotent cell derived from a second non-human animal into an embryo derived from a first non-human animal, said embryo being at a cleavage stage and having a genome in which a function of nanos3 gene is inhibited, to prepare a chimeric embryo, and allowing said chimeric embryo to develop into an individual.