title: Human cancer growth and therapy in immunodeficient mouse models.
abstract: Since the discovery of the "nude" mouse more than 40 years ago, investigators have attempted to model human tumor growth in immunodeficient mice. Here, we summarize how the field has advanced over the ensuing years owing to improvements in the murine recipients of human tumors. These improvements include the discovery of the scid mutation and development of targeted mutations in the recombination-activating genes 1 and 2 (Rag1(null), Rag2(null)) that severely cripple the adaptive immune response of the murine host. More recently, mice deficient in adaptive immunity have been crossed with mice bearing targeted mutations designed to weaken the innate immune system, ultimately leading to the development of immunodeficient mice bearing a targeted mutation in the gene encoding the interleukin 2 (IL2) receptor common γ chain (IL2rg(null), also known in humans as cytokine receptor common subunit γ). The IL2rg(null) mutation has been used to develop several immunodeficient strains of mice, including the NOD-scid IL2rg(null) (NSG) strain. Using NSG mice as human xenograft recipients, it is now possible to grow almost all types of primary human tumors in vivo, including most solid tumors and hematological malignancies that maintain characteristics of the primary tumor in the patient. Programs to optimize patient-specific therapy using patient-derived xenograft tumor growth in NSG mice have been established at several institutions, including The Jackson Laboratory. Moreover, NSG mice can be engrafted with functional human immune systems, permitting for the first time the potential to study primary human tumors in vivo in the presence of a human immune system.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609;
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609;
authors.forename: Neal
authors.initials: N
authors.lastname: Goodwin
authors.affiliation: The Laboratory for Human Disease Models, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan;
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishikawa
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609;
authors.forename: Vishnu
authors.initials: V
authors.lastname: Hosur
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609;
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Lyons
authors.affiliation: University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007107:Immune System / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D012106:Research / Q000639:trends; D014183:Transplantation, Heterologous / Q000639:trends