Immune Cell-Engrafted Non-Human Animals and Non-Human Animal Models
AssigneeLapix Therapeutics, Inc.
InventorsAnas Fathallah, Abdulraouf Ramadan
Life of this patent
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Abstract
The disclosure provides, in various embodiments, non-human animals that comprise a human immune cell engraftment and/or functional human immune system. The disclosure also provides, in various embodiments, methods of generating said non-human animals. The disclosure also provides, in various embodiments, methods of determining immunogenicity of antigens or an immunogenic fragment thereof or antigenic therapies and/or identifying agents that modulate immune response.
Claims84
A non-human animal, wherein the non-human animal:
- a) lacks endogenous mature T cells;
- and
- b) comprises an engrafted population of human mononuclear cells, human polymorphonuclear leukocytes, or both, wherein the engraftment lacks human cancer cells.
A non-human animal, wherein the non-human animal:
- a) lacks endogenous mature T cells;
- and
- b) comprises a functional human immune system generated from an engraftment of a population of human mononuclear cells, human polymorphonuclear leukocytes, or both, wherein the engraftment lacks human cancer cells.
A method of generating a non-human animal, comprising engrafting a population of human mononuclear cells, human polymorphonuclear leukocytes, or both into a non-human animal lacking endogenous mature T cells, wherein the engraftment lacks human cancer cells.
A method of generating a non-human animal, comprising engrafting a population of human mononuclear cells, human polymorphonuclear leukocytes, or both into a non-human animal lacking endogenous mature T cells, wherein the engraftment lacks human cancer cells, and wherein the engraftment produces a functional human immune system in the non-human animal.
The method of any one of claims 3-662, further comprising incubating the population of human mononuclear cells, human polymorphonuclear leukocytes, or both with a TIM receptor agonist.
A method of generating a non-human animal model, comprising
- for n individual non-human animals lacking endogenous mature T cells, engrafting a population of human mononuclear cells, human polymorphonuclear leukocytes, or both from a nth human into a nth non-human animal, wherein n is an integer ≥2,
- thereby generating a non-human animal model comprising two or more individual non-human animals,
- wherein the engraftments lack human cancer cells and produce a functional human immune system in the individual non-human animals.
A non-human animal, wherein the non-human animal:
- a) lacks endogenous mature T cells, endogenous mature B cells, and endogenous mature NK cells;
- b) comprises an engrafted population of human mononuclear cells, human polymorphonuclear leukocytes, or both, wherein the engraftment lacks human cancer cells, and wherein the population of human mononuclear cells comprises human T cells, human B cells, human NK cells, human monocytes, and human macrophages;
- c) expresses human IL-3, human GM-CSF, and human SF;
- d) lacks Rag1 expression, function, or both;
- and
- e) lacks IL2rγ expression, function, or both.
Dependencies are inferred from the claim text.