Modeling Human Cancer in Mice 40x 10x .Modeling Human Cancer in Mice Xenograft Models Xenograft Host

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  • Modeling Human

    Cancer in Mice 40x

    10x

    Presented by:

    Brian W. Soper, PhD

    Technical Information Services

    Hosted by Charles River, exclusive

    distributor of JAX Mice in 27 European

    Countries

  • The Jackson Laboratorys Mission

    2

    Performing Research

    Investigating genetics and biology of human disease

    Providing Resources

    JAX Mice Clinical & Research Services, bioinformatics data,

    technical publications and more

    Educating Scientists

    World-class courses, internships and other programs

    www.jax.org/courses |

    http://www.jax.org/courses

  • JAX Mice The Gold Standard for Biomedical Research

    JAX Mice The Gold Standard for Biomedical Research

    3

    NIH funded resource

    >7,000 strains and growing

    o 2.7 million mice shipped annually

    Unsurpassed genetic quality & animal health

    Best characterized & referenced ~100 new pubs/week

    Common inbred strains (C57BL/6J, BALB/cJ, DBA/2J) support

    development/collection of specialty strains and other valuable

    community research resources

    JAX Mice |

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Online Resources to Expedite

    Research

    4

    JAX Mice Database

    www.jax.org/jaxmice

    www.jax.org/jaxmice/support/techsupport-index |

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmice/support/techsupport-indexhttp://www.jax.org/jaxmice/support/techsupport-indexhttp://www.jax.org/jaxmice/support/techsupport-index

  • Online Resources to Expedite

    Research

    5

    JAX Mice Database

    www.jax.org/jaxmice

    Mouse Genome Informatics

    www.informatics.jax.org

    www.jax.org/jaxmice/support/techsupport-index |

    http://www.jax.org/jaxmicehttp://www.informatics.jax.orghttp://www.jax.org/jaxmice/support/techsupport-indexhttp://www.jax.org/jaxmice/support/techsupport-indexhttp://www.jax.org/jaxmice/support/techsupport-index

  • Online Resources to Expedite

    Research

    6

    JAX Mice Database

    www.jax.org/jaxmice

    Mouse Genome Informatics

    www.informatics.jax.org

    Mouse Phenome Database

    www.jax.org/phenome

    And many more unique

    resources

    www.jax.org/jaxmice/support/techsupport-index |

    http://www.jax.org/jaxmicehttp://www.informatics.jax.orghttp://www.jax.org/phenomehttp://www.jax.org/jaxmice/support/techsupport-indexhttp://www.jax.org/jaxmice/support/techsupport-indexhttp://www.jax.org/jaxmice/support/techsupport-index

  • ACS Cancer Incidence USA Statistics through 2011

    7

    www.cancer.org/research/cancerfactsfigures

    Females Males

    Rate

    per

    100,0

    00

    Lung

    1970 2011

    Prostate

    20

    40

    60

    80

    20

    40

    60

    80

    1970 2011

    Breast Lung

    JAX Mice |

    http://www.cancer.org/Research/CancerFactsStatistics/cancerfactsfigures2015/cancer-facts-and-figures-2015http://www.cancer.org/Research/CancerFactsStatistics/cancerfactsfigures2015/cancer-facts-and-figures-2015http://www.cancer.org/Research/CancerFactsStatistics/cancerfactsfigures2015/cancer-facts-and-figures-2015http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Modeling Human Cancer in Mice

    Xenograft Models

    Xenograft Host Selection

    Spontaneous and Inducible Models

    Online Data and Resources

    JAX Mice | 8

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Utilizing Xenograft Models

    Xenograft Sample

    o Established cell lines

    o Primary cell lines

    o Patient derived tumor tissue

    Immunodeficient Hosts

    o Nude

    o NOD-scid

    o NOD-scid gamma (NSG)

    JAX Mice | 9

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Utilizing Xenograft Models

    Xenograft Sample

    o Established cell lines

    o Primary cell lines

    o Patient derived tumor tissue

    Immunodeficient Hosts

    o Nude

    o scid

    o NOD-scid gamma (NSG)

    JAX Mice | 10

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • JAX Mice | 11

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Immune System Components

    JAX Mice | 12

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Inbred and Outbred Nude Mice

    Mouse Nomenclature

    Inbred Nude NU/J (002019)

    Outbred Nude J:NU (007850)

    Immunological Deficiencies

    Mutation: Foxn1nu

    Athymic and T cell Deficient

    Flanagan SP. 1966. Genet Res 8(3):295-309. PMID:5980117

    Pantelouris EM. 1973. Differentiation 1(6):437-50. PMID:4547146

    JAX Mice | 13

    http://jaxmice.jax.org/strain/002019.htmlhttp://jaxmice.jax.org/strain/007850.htmlhttp://www.ncbi.nlm.nih.gov/pubmed?term=5980117http://www.ncbi.nlm.nih.gov/pubmed?term=4547146http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Inbred and Outbred Nude Mice

    Mouse Nomenclature

    Inbred Nude NU/J (002019)

    Outbred Nude J:NU (007850)

    Immunological Deficiencies

    Mutation: Foxn1nu

    Athymic and T cell Deficient

    Applications and Benefits

    Engraftment of human & mouse tumor cell lines

    Well published/characterized

    Hairless phenotype enhances assessment of tumor growth

    Flanagan SP. 1966. Genet Res 8(3):295-309. PMID:5980117

    Pantelouris EM. 1973. Differentiation 1(6):437-50. PMID:4547146

    JAX Mice | 14

    http://jaxmice.jax.org/strain/002019.htmlhttp://jaxmice.jax.org/strain/007850.htmlhttp://www.ncbi.nlm.nih.gov/pubmed?term=5980117http://www.ncbi.nlm.nih.gov/pubmed?term=4547146http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Immune System Components

    JAX Mice | 15

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Easy Evaluation of Therapeutic

    Response in Nude Mice

    Gulliya KS et al. 1994. Cancer 74(6):1725-32. PMID:8082074

    Before treatment After treatment

    JAX Mice | 16

    http://www.ncbi.nlm.nih.gov/pubmed?term=8082074http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Nude Mice

    Mouse Nomenclature

    Inbred Nude NU/J (002019)

    Outbred Nude J:NU (007850)

    Immunological Deficiencies

    Mutation: Foxn1nu

    Athymic and T cell deficient

    Considerations

    Innate immunity intact

    Not useful for hematopoietic cancer models

    Not suitable for primary cell transplantation

    Flanagan SP. 1966. Genet Res 8(3):295-309. PMID:5980117

    Pantelouris EM. 1973. Differentiation 1(6):437-50. PMID:4547146

    17 JAX Mice |

    http://jaxmice.jax.org/strain/002019.htmlhttp://jaxmice.jax.org/strain/007850.htmlhttp://www.ncbi.nlm.nih.gov/pubmed?term=5980117http://www.ncbi.nlm.nih.gov/pubmed?term=4547146http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • BALB/c-scid

    Mouse Nomenclature

    CBySmn.CB17-Prkdcscid/J (001803)

    o Similar to original C.B-17 scid

    Immunological Deficiencies

    Mutation: scid severe combined immune deficiency

    No mature B and T cells

    JAX Mice | 18

    http://jaxmice.jax.org/strain/001803.htmlhttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • BALB/c-scid

    Mouse Nomenclature

    CBySmn.CB17-Prkdcscid/J (001803)

    o Similar to original C.B-17 scid

    Immunological Deficiencies

    Mutation: scid severe combined immune deficiency

    No mature B and T cells

    Applications

    Xenograft host for cancer cell lines

    Efficacy testing of therapeutic antibodies (CDC and ADCC intact)

    Adoptive transfer from BALB/c donors

    Infectious disease

    Common inbred background simplifies creation of compound

    immunodeficient mutants

    JAX Mice | 19

    http://jaxmice.jax.org/strain/001803.htmlhttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Immune System Components

    JAX Mice | 20

    http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • BALB/c-scid

    Therapeutic Ab/Fusion Protein Efficacy

    Shin S et al. 2011. Mol Cancer Ther 10:603-614. PMID:21393427

    JAX Mice | 21

    Human SK-BR-3 Breast Cancer Cells

    http://www.ncbi.nlm.nih.gov/pubmed?term=21393427http://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmicehttp://www.jax.org/jaxmice

  • Mouse Nomenclature CBySmn.CB17-Prkdcscid/J (001803) o Similar to original C.B-17 scid

    Applications Xenograft host for cancer cell lines

    Efficacy testing of therapeutic antibodies

    Adoptive transfer from BALB/c donors

    Common inbred background simplifies creation of compound immunodeficient mutants

    Considerations Innate immunity intact

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