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Transcript
Oncology
MODELS AND SERVICES DESIGNED
TO TAKE YOUR STUDY FURTHER
ONCOLOGY
TACONIC BIOSCIENCES
Oncology
Evaluating the response of translational
rodent models to new cancer therapies
is the key to developing innovative
treatment options.
The super immunodeficient
CIEA NOG mouse® is the
ideal model for engraftment
of human cells, and therefore
the model of choice for
combined immune system
and tumor engraftment
immuno-oncology
experiments.
Taconic Biosciences offers a
comprehensive portfolio of translational
rodent models to accelerate and enhance
your research in the field of oncology.
Mouse models available exclusively
from Taconic include human immune
system engrafted mice for tumor grafting
and therapeutics testing, spontaneous
tumor models for breast and colon
cancer research, and a wide variety of
immunodeficient mice, including the
super immunodeficient CIEA NOG
mouse®. Taconic also provides integrated
model generation and breeding services
to accelerate drug discovery and
development timelines.
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Oncology | 2
ONCOLOGY
TACONIC BIOSCIENCES
TABLE OF
CONTENTS
HUMAN IMMUNE SYSTEM ENGRAFTED MODELS�������������������������������������������������������������������5
SUPER IMMUNODEFICIENT NOG MODELS��������������������������������������������������������������������������������7
IMMUNODEFICIENT MODELS�����������������������������������������������������������������������������������������������������������9
Nudes������������������������������������������������������������������������������������������������������������������������������������������������������ 9
SCIDs������������������������������������������������������������������������������������������������������������������������������������������������������� 11
Rag2 Models���������������������������������������������������������������������������������������������������������������������������������������� 12
MODELS WITH MULTIPLE IMMUNODEFICIENCIES��������������������������������������������������������������� 13
MODELS FOR SYNGENEIC TUMOR EXPERIMENTS�������������������������������������������������������������� 14
SPONTANEOUS TUMOR MODELS������������������������������������������������������������������������������������������������ 16
COMPARISON CHART OF ONCOLOGY MOUSE AND RAT MODELS����������������������������20
INTEGRATED CUSTOM MODEL GENERATION AND BREEDING SOLUTIONS����������� 21
TO ORDER
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ONCOLOGY
TACONIC BIOSCIENCES
TACONI C OF F ER S
HUM AN I M M U NE SYSTEM
E NGRAF TED M OD EL S
CIEA
NOG
mouse ®
Immunodeficient mice carrying a
reconstituted human immune system
The super immunodeficient CIEA
NOG mouse® is the ideal model
for engraftment of human cells,
and therefore the model of choice
for combined immune system
and tumor engraftment immunooncology experiments.
When reconstituted with various human
tissue sources, NOG mice are indispensable
for basic research probing the human
immune system. Engrafted NOG mice enable
efficacy testing of immunotherapies as
well as the unprecedented ability to study
tumor specific modulation of the immune
system. Taconic offers study-ready cohorts of
hematopoietic stem cell-engrafted NOG mice.
In addition to these models, Taconic offers
access to scientific expertise on use of
the CIEA NOG mouse® for engraftment
and reconstitution with human tissues.
HOW CAN IMMUNE SYSTEM
ENGRAFTED NOG MICE BE USED?
Immune system engrafted mouse models
are excellent tools to evaluate the effect
of human immune cells in preclinical
oncology:
• Assessment of therapeutic
immunomodulatory activities
• Evaluation of antitumor activity
related to antibody dependent
cell cytotoxicity (ADCC)
• Analysis of innate and
adaptive immunity
• Cytokine readouts
These models are also excellent tools
for other research application, such as:
• Immuno-Oncology Research
• GvHD (Graft versus Host Disease)
• T cell activation model
• B cell depletion studies
• Autoimmune disease
• Allergy
• Inflammation
• HIV Research
• Vaccine development
• Transplantation
• Study of hematopoiesis
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Oncology | 4
ONCOLOGY
TACONIC BIOSCIENCES
huPBMC-NOG
NOG MICE ENGRAFTED WITH HUMAN
PBMCs (PERIPHERAL BLOOD MONONUCLEAR CELLS)
• Model for investigation of adult/
mature cell populations.
• Use is limited to short term studies.
• GvHD response can be used as a
screening system for T cell
modulating drugs.
• Available with normal or patientderived PBMCs.
huNOG
NOG MICE ENGRAFTED WITH HUMAN
CD34 + HEMATOPOIETIC STEM CELLS (HSCs)
• Stable engraftment of multiple
cell lineages by 12-16 weeks
post-injection.
• Only mice with ≥25% hCD45+ in
peripheral blood are delivered.
• Long-term studies possible.
huNOG MICE ARE AVAILABLE
OFF-THE-SHELF! PLACE YOUR ORDER
NOW FOR IMMEDIATE DELIVERY.
huNOG-EXL
NOG-EXL (HGM-CSF/HIL3-NOG) MICE ENGRAFTED WITH
HUMAN CD34 + HEMATOPOIETIC STEM CELLS (HSCs)
• Stable engraftment of multiple cell
lineages, with improved myeloid cell
differentiation.
• Only mice with ≥25% hCD45+ in
peripheral blood are delivered.
• Long-term engraftment enables
long-term studies.
huNOG-EXL MICE ARE AVAILABLE
OFF-THE-SHELF! PLACE YOUR ORDER
NOW FOR IMMEDIATE DELIVERY.
LICENSING: NO MTA OR LICENSE FEE
IS REQUIRED FOR ANY OF THE
MODELS FEATURED ON THIS PAGE.
TO ORDER
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ONCOLOGY
TACONIC BIOSCIENCES
H E M ATO P O IE S IS A ND HUM AN
I M M U N E SYST E M ENG RAFTED MICE
HEMATOPOIETIC
STEM CELL
IL-1
IL-3
GM-CSF
SCF
COMMON LYMPHOID
PROGENITOR
COMMON MYELOID
PROGENITOR
IL-2
IL-7
IL-12
SDF-1
GM-CSF
IL-1 IL-6
IL-2 IL-7
IL-4
MYELOBLAST
TNK PROGENITOR
B LYMPHOCYTE
SCF
G-CSF
GM-CSF
IL-3
IL-6
BASOPHIL
SCF
G-CSF
GM-CSF
IL-3
IL-6
GM-CSF
IL-3
IL-5
NEUTROPHIL EOSINOPHIL
huNOG-EXL
(hGM-CSF/hIL-3 NOG)
SCF
M-CSF
G-CSF
GM-CSF
IL-3
IL-6
MONOCYTE
hIL-6 NOG
IL-2
IL-7
IL-15
IL-7
NK CELL
hIL-2 NOG, hIL-15 NOG
T LYMPHOCYTE
huNOG
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Oncology | 6
ONCOLOGY
TACONIC BIOSCIENCES
S U PE R I MMU NO DEF ICIENT
N O G M O DE LS
CIEA NOG mouse®
N OM EN CLATURE
T, B & NK CELL DEFICIENT MOUSE
WITH IMPAIRED MYELOID FUNCTIONS
• The CIEA NOG mouse® is a super
immune deficient mouse with
unparalleled potential to engraft human
cells and tissues.
• This severely immunocompromised
mouse carries the scid mutation and a
targeted mutation of the Il2rg gene on
the NOD/ShiJic genetic background.
• The functional knockout of the IL2
receptor common gamma chain
(IL2rg) results in reduction of residual
innate immunity of the NOD/ShiJic
background and superior engraftment
of human cells and tissues compared to
any other immune deficient model.
• Lack of mature T, B and NK cells,
reduced complement activity, dysfunctional macrophages and dendritic cells,
and deficiencies in immune signaling,
including impaired cytokine production.
NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac
• The polymorphism of Sirpa allows the
mouse SIRPA to bind human CD47,
preventing activation of recipient
macrophages to engulf human cells
therefore making it an ideal model for
human immune system engraftment
and PDX.
• Excellent choice for xenograft studies
using cell lines with poor take rates in
nudes or scids, or for engraftment of
patient-derived tumors.
• The best choice for human immune
system engraftment mice, with
successful engraftment of various
tissues such as PBMCs or umbilical
cord blood stem cells.
• Test therapeutic antibodies and
immune-modulating treatments
by combining immune system
engraftment of the immune system
with xenograft of tumor cell lines or
patient-derived tumors.
• Displays a very low incidence of
lymphoma, unlike NOD scid model.
• The Il2rg gene is X-linked, so male
knockouts are hemizygous for the Il2rg
mutant allele.
• Sponsored by the Central Institute for
Experimental Animals (CIEA) and
In-Vivo Science International.
• Applications in research involving
cancer, infectious disease (HIV,
malaria), immuno-oncology, CAR-T,
iPS, and humanization immune system
engraftment.
• Now available pre-engrafted with
human hematopoietic stem cell (hHSC)
as huNOG for immediate delivery at
16 weeks post-engraftment.
MODEL NUMBER NOG
NOG-EXL (hGM-CSF/hIL-3 NOG)
T, B & NK CELL DEFICIENT MOUSE
WITH IMPAIRED MYELOID FUNCTIONS
• NOG mouse expressing human
GM-CSF and IL-3.
• Supports higher overall engraftment
and superior myeloid cell differentiation
after human HSC engraftment.
• Now available pre-engrafted with HSCs
as huNOG-EXL for immediate delivery
at 10 weeks post-engraftment.
N OM EN CLATURE
NOD.Cg-Prkdcscid Il2rgtm1Sug
Tg(SV40/HTLV-IL3,CSF2)10-7Jic/JicTac
• May be a suitable host for human acute
myeloid leukemia (AML) xenografts
that are dependent on human GM-CSF
and human IL-3.
• The polymorphism of Sirpa allows the
mouse SIRPA to bind human CD47,
preventing activation of recipient
macrophages to engulf human cells
therefore making it an ideal model for
human immune system engraftment
and PDX.
• Excellent choice for xenograft studies
using cell lines with poor take rates in
nudes or scids, or for engraftment of
patient-derived tumors that requires
human GM-CSF or human IL-3.
MODEL NUMBER 13395
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ONCOLOGY
TACONIC BIOSCIENCES
hIL-2 NOG
N OMENCLATURE
T, B & NK CELL DEFICIENT MOUSE WITH
IMPAIRED MYELOID FUNCTIONS
• NOG mouse expressing human IL-2
cytokine.
• Predominant differentiation of human
NK cells following hHSC engraftment.
NOD.Cg-Prkdcscid Il2rgtm1Sug
Tg(CMV-IL6)4-2Jic/JicTac
• Excellent choice for xenograft studies
using cell lines with poor take rates
in nudes or scids, or for engraftment
of patient-derived tumors or tumor
infiltrating lymphocytes that requires
human IL-2.
MODEL NUMBER 13440
hIL-6 NOG
N OMENCLATURE
T, B & NK CELL DEFICIENT MOUSE WITH
IMPAIRED MYELOID FUNCTIONS
• NOG mouse expressing human IL-6
cytokine.
• Enhanced expansion of human
monocytes following hHSC
engraftment.
NOD.Cg-Prkdcscid Il2rgtm1Sug
Tg(CMV-IL6)1-1Jic/JicTac
• May be a suitable host for human IL-6
dependent tumor such as multiple
myeloma (MM) xenografts.
MODEL NUMBER 13686
hIL-15 NOG
N OMENCLATURE
T, B & NK CELL DEFICIENT MOUSE WITH
IMPAIRED MYELOID FUNCTIONS
• NOG mouse expressing human IL-15
cytokine.
NOD.Cg-Prkdcscid Il2rgtm1Sug
Tg(CMV-IL2/IL15)1-1Jic/JicTac
• Engraftment and expansion of human
NK cells following engraftment with
CD56+ NK cells derived from PBMC.
MODEL NUMBER 13683
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IS REQUIRED FOR ANY OF THE
MODELS FEATURED ON THIS PAGE.
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Oncology | 8
ONCOLOGY
TACONIC BIOSCIENCES
IM M UNO DE FIC IENT M OD ELS
NUDES
THE AUTOSOMAL RECESSIVE NUDE GENE IN HOMOZYGOUS (NU/NU) MICE CAUSES THE
LACK OF FUR AND AN ABNORMAL THYMUS. HETEROZYGOUS (NU/+) ANIMALS CARRY
ONLY ONE COPY OF THE NUDE MUTATION AND HAVE HAIR. HETEROZYGOUS NUDES
WERE ORIGINALLY THOUGHT TO HAVE NORMAL IMMUNE SYSTEMS, BUT IN FACT HAVE
IMMUNE ALTERATIONS SUCH AS REDUCED BONE MARROW STEM CELLS AND LOWER
THYMUS WEIGHTS. HETEROZYGOUS NUDES MAY BE USED IN PK/DOSING STUDIES.
B6 nude
N OM EN CLATURE
B6.Cg/NTac-Foxn1nu NE10
T CELL DEFICIENT MOUSE
• Foxn1nu mutation backcrossed to
the C57BL/6NTac inbred strain for
ten generations.
MODEL NUMBER B6NU
BALB/c nude
N OM EN CLATURE
C.Cg/AnNTac-Foxn1nu NE9
T CELL DEFICIENT MOUSE
• Foxn1nu mutation backcrossed to
the BALB/cAnN inbred strain for
nine generations.
MODEL NUMBER BALBNU
NCr nude
N OM EN CLATURE
CrTac:NCr-Foxn1nu
T CELL DEFICIENT MOUSE
• Outbred background originated
from an accidental cross between
the BALB/c inbred nude and NIH(S)
outbred nude mice.
• The standard athymic model for
National Cancer Institute (NCI) studies
as well as many pharmaceutical
and institutional oncology
screening programs.
MODEL NUMBER NCRNU
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ONCOLOGY
TACONIC BIOSCIENCES
NIH nude
N OMENCLATURE
NTac:NIH-Foxn1rnu
T CELL DEFICIENT RAT
• This immunodeficient rat model is ideal
for studies requiring a larger tumor
burden, studies which require imaging
or studies which bridge oncology
efficacy and PK/PD.
• In this outbred immunodeficient
model the vibrissae are present in the
homozygous nude rat, but they are
bent, with some short hairs on the
head and occasionally on the rest
of the body.
• Good xenograft host for many cell lines.
MODEL NUMBER NIHRNU
NMRI nude
N OMENCLATURE
BomTac:NMRI-Foxn1nu
T CELL DEFICIENT MOUSE
• Foxn1nu mutation backcrossed
to the NMRI outbred stock.
• Widely-used as host for transplanted
human tumors and for therapeutic
studies on human tumors.
• The NMRI nude has a relatively low
take-rate for human breast tumors
compared to other nude
or immunodeficient mice.
MODEL NUMBER NMRINU
HRN™ nude
N OMENCLATURE
CrTac:NCr-Portm1Wolf Foxn1nu Tg(Alb-cre)21Mgn
T CELL DEFICIENT MOUSE
• The combination of the nude mutation
and the HRN™ mutations permits
xenograft studies in a mouse without
liver P450 metabolism.
• Useful when studying highly cleared
chemotherapeutics, allowing efficacy
testing without the need for multiple
dosing or the use of constant
infusion pumps.
• Used to get a quick readout on the
efficacy of your anticancer lead
compounds without having to first
work through PK issues.
• A combination between Taconic’s
leading outbred nude, the NCr nude,
and the HRN™ transgenic mouse.
MODEL NUMBER 9066
CRYOP RES ERVED
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Oncology | 10
ONCOLOGY
SCIDs
TACONIC BIOSCIENCES
SEVERE COMBINED IMMUNODEFICIENCY
MICE HOMOZYGOUS FOR THE Prkdc scid MUTATION LACK BOTH T AND B CELLS DUE
TO A DEFECT IN V(D)J RECOMBINATION. THIS FEATURE MAKES THESE MODELS
IDEAL FOR ACCEPTING FOREIGN TISSUE TRANSPLANTS, INCLUDING HUMAN TUMORS.
THESE MODELS ARE USED FOR TESTING NEW CANCER TREATMENTS,
AND AS HOSTS FOR HUMAN IMMUNE SYSTEM TISSUES (I.E. SCID-HU).
C.B-17 scid
N OM EN CLATURE
C.B-Igh-1b/IcrTac-Prkdcscid
T & B CELL DEFICIENT MOUSE
• The original congenic background
strain on which Dr. Mel Bosma
discovered the spontaneous scid
mutation.
• Available at two health designations:
Defined Flora from gnotobiotic
isolators and Restricted Flora™ from
Isolated Barrier Units™.
MODEL NUMBER CB17SC
ICR scid
N OM EN CLATURE
T & B CELL DEFICIENT MOUSE
IcrTac:ICR-Prkdcscid
• Equivalent to the C.B-17 scid in severity
of immunodeficiency, but this outbred
background exhibits a significantly
reduced incidence of spontaneous Ig
production (leakiness).
MODEL NUMBER ICRSC
NOD scid
N OM EN CLATURE
T & B CELL DEFICIENT MOUSE
• The scid mutation has been transferred
onto a diabetes-susceptible Non-Obese
Diabetic (NOD).
NOD/MrkBomTac-Prkdcscid
• The multiple defects in immunity
unique to this model provide a very
good system for reconstitution with
human hematopoietic cells, resulting in
excellent models for HIV-1 research and
gene therapy.
• Useful model for investigating
increased tumor incidence, particularly
lymphomas and thymic tumors.
• Short life span of ~8-9 months due to
lethal thymic lymphomas.
• Does not develop spontaneous diabetes.
MODEL NUMBER NODSC
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ONCOLOGY
TACONIC BIOSCIENCES
Rag2 MODELS
MICE HOMOZYGOUS FOR THE RAG2 NULL MUTATION EXHIBIT TOTAL INABILITY TO INITIATE V(D)J REARRANGEMENT
AND FAIL TO GENERATE MATURE T OR B LYMPHOCYTES. NEVERTHELESS, THE RAG2 MOUSE HAS APPARENTLY NORMAL
HEMATOPOIESIS. RAG2 KNOCKOUTS ARE USEFUL FOR VACCINE DEVELOPMENT, TRANSPLANTATION OR XENOGRAFT
STUDIES, AND HEMATOPOIESIS RESEARCH. THE RAG2 MOUSE IS USEFUL IN EVALUATING THE FUNCTION OF SPECIFIC
GENES AS THEY RELATE TO BONE MARROW TRANS-COMPLEMENTATION ASSAYS.
Rag2 (129S6)
T & B CELL DEFICIENT MOUSE
N OMENCLATURE
129S6/SvEvTac-Rag2tm1Fwa
• The 129S6 strain was the original strain in which the
Rag2 targeted mutation was created.
MODEL NUMBER RAG2
CRYOP RES ERVED
Rag2 (BALB/c)
T & B CELL DEFICIENT MOUSE
N OMENCLATURE
C.129S6(B6)-Rag2tm1Fwa N12
• Backcrossed twelve generations (N12) to the
BALB/cAnNTac inbred strain.
MODEL NUMBER 601
Rag2 (B6.SJL)
T & B CELL DEFICIENT MOUSE
N OMENCLATURE
B6.SJL(129S6)-Ptprca/BoyCrTac Rag2tm1Fwa N10
• Similar to C57BL/6 with the H2b haplotype, but carries
the Ptprca and Pep3b genes from the SJL strain (CD45.1).
MODEL NUMBER 461
CRYOP RES ERVED
Rag2 (C57BL/6)
T & B CELL DEFICIENT MOUSE
N OMENCLATURE
B6.129S6-Rag2tm1Fwa N12
• Backcrossed twelve generations (N12) to the
C57BL/6NTac inbred strain.
MODEL NUMBER RAGN12
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Oncology | 12
ONCOLOGY
TACONIC BIOSCIENCES
M O D E L S W IT H MU LT IPLE
IMM UNO DEF IC IE NC IES
Scid-beige
N OM EN CLATURE
T, B & NK CELL DEFICIENT MOUSE
• The mutations were backcrossed
seven generations to the congenic
C.B-17 background.
C.B-Igh-1b/GbmsTac-Prkdcscid Lystbg N7
• This double mutant model carries the
scid mutation which causes a lack of
both T and B lymphocytes due to a
defect in V(D)J recombination.
• It also carries the beige mutation
which results in cytotoxic T cell
and macrophage defects as well
as selective impairment of
NK cell functions.
MODEL NUMBER CBSCBG
Rag2/Il2rg Double
Knockout Mouse
N OM EN CLATURE
B10;B6-Rag2tm1Fwa Il2rgtm1Wjl
T, B & NK CELL DEFICIENT MOUSE
• Useful for transplanting allogeneic or
xenogeneic stem cells, which are
often rejected by NK cells.
• May be used in combination with
parent Rag2 knockout model for
defining the role of NK cells in
host resistance to tumors and
infectious agents.
• May not be the best choice for
experiments involving humanization
of the immune system, since human
hematopoietic stem cells do
not engraft and differentiate well
in strains on B6 or B6-related
backgrounds.
• The Il2rg gene is located on the X
chromosome, so male knockouts
are hemizygous for the Il2rg
mutant allele.
MODEL NUMBER 4111
CIEA BRG mouse
N OM EN CLATURE
T, B & NK CELL DEFICIENT
• Higher radiation tolerance due to Rag2
mutation compared to scid models
(similar to wild type mice).
• Model is completely congenic on
BALB/c background, the preferred
strain background for many
immunology studies.
C.Cg-Rag2tm1Fwa Il2rgtm1Sug/JicTac
• Applications in studies on immune
system engraftment, infectious
diseases, and autoimmune diseases as
well as cancer xenografts.
• Sponsored by the Central Institute
for Experimental Animals and In-Vivo
Science International.
MODEL NUMBER 11503
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ONCOLOGY
TACONIC BIOSCIENCES
M O D E LS FO R SYNG ENEIC
TU M O R E X P ERIMENTS
WITH THE GROWTH IN IMMUNO-ONCOLOGY RESEARCH, SYNGENEIC MODELS ARE INCREASING IN POPULARITY.
IN A SYNGENEIC TUMOR EXPERIMENT, A MOUSE TUMOR OR CELL LINE IS ENGRAFTED ONTO A WILD TYPE
MOUSE OF THE SAME BACKGROUND STRAIN. AS THE HOST HAS A FULLY COMPETENT IMMUNE SYSTEM, THESE
TYPES OF EXPERIMENTS ARE IDEAL FOR EVALUATION OF IMMUNO-ONCOLOGY THERAPEUTICS.
C57BL/6
INBRED STRAIN
• One of the most commonly used
inbred strains for syngeneic tumor
experiments, with a wide variety of
C57BL/6-derived cell lines available.
• May be used in combination with
immunodeficients on C57BL/6
background (B6 nude, Rag2 knockout,
Rag2/Il2rg (B10;B6)), with labeled
strains (B6.SJL-Ptprca, OT-I or OT-II TCR
transgenics), B6 albino, Diet Induced
Obese Black 6 mice and many other
GEM models.
• Common cell lines: Breast (E0771),
Colon (MC-38), Liver (Hep-55.1C),
Lung (LLC1), Melanoma (B16,
B16F10), Pancreas (Panc02), Prostate
(Tramp-C1/2).
• Available as SPF (Murine Pathogen
Free™), SOPF (Excluded Flora) and as
axenic (Germ Free).
• Immunology: Th1-biased.
MODEL NUMBER B6
N OMENCLATURE
C57BL/6NTac
MODEL NUMBER B6JBOM
N OMENCLATURE
C57BL/6JBomTac
BALB/c
INBRED STRAIN
• One of the most commonly used
inbred strains for syngeneic tumor
experiments, with a wide variety of
BALB/c-derived cell lines available.
• May be used in combination with
immunodeficients on BALB/c
background (BALB/c nude, Rag2
knockout, CIEA BRG mouse).
• Immunology: Th2-biased.
MODEL NUMBER BALB
• Common cell lines: Breast (4T1,
MC4), Colon (CT26), Kidney (RenCa),
Lymphoma (A20).
• Available as SPF (Murine Pathogen
Free™), SOPF (Excluded Flora) and as
axenic (Germ Free).
N OMENCLATURE
BALB/cAnNTac
MODEL NUMBER BALJBO
N OMENCLATURE
BALB/cJBomTac
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Oncology | 14
ONCOLOGY
TACONIC BIOSCIENCES
C3H
N OM EN CLATURE
C3H/HeNTac
INBRED STRAIN
• General purpose strain, widely used in
cancer research.
• Immunology: Th1-biased.
• Common cell lines: Bladder (MBT-2),
Head and Neck (SCC-7), Lymphoma
(38C13) Breast (CaD2).
• Available as SOPF (Excluded Flora).
MODEL NUMBER C3H
DBA/2
N OM EN CLATURE
DBA/2NTac
INBRED STRAIN
• General purpose strain, differs widely
from C57BL/6 in many genetic loci.
• Immunology: Th2-biased, Complement
C5-deficient.
• Common cell lines: Leukemia (L1210),
Lung (KLN-205) Melanoma (Cloudman
S91).
• Available as SPF (Murine Pathogen Free™).
MODEL NUMBER DBA2
TACONIC ALSO OFFERS THE DBA/1, SJL AND FVB STRAINS, WHICH ARE OCCASIONALLY USED IN
SYNGENEIC TUMOR MODELS.
Cancer and the microbiome
Recent studies have identified a link between cancer and the microbiome, including
differential response to immuno-oncology therapies. Taconic offers the most advanced
portfolio of animal models and services for microbiome research, including:
• Commercially available germ-free mice: C57BL/6, BALB/c, Swiss Webster
• Germ-free derivations
• Association of germ-free mice with client-provided microbiota
• Range of available husbandry options for large or small study cohorts and
short- or long-term animal studies including semi-rigid isolators and individually
ventilated cages (IVCs)
• Biospecimen collection
• Shipment of conditioned animals or samples to client or CRO at study end
Taconic shares its decades of experience in germ-free husbandry via educational
support materials. Visit taconic.com/microbiome.
TO ORDER
15 | Oncology
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ONCOLOGY
TACONIC BIOSCIENCES
S PO NTANEO U S
T UM OR MO DEL S
Invasive Lobular
Breast Cancer Model
BREAST CANCER MODEL
• Tissue-specific conditional knockout
of Cdh1 (E-cadherin) and Trp53 in
mice induces metastatic mammary
carcinomas that resemble human
invasive lobular carcinoma (ILC), the
second most common type of primary
breast cancer.
• From the literature, it is estimated
that females develop multiple skin
and mammary tumors with a median
latency of 214 days.
N OMENCLATURE
FVB.Cg-Cdh1tm1Jjon Trp53tm1Brn
Tg(KRT14-cre)8Brn/A
• Can be used to supply tumor tissues
for allografts.
• 20-30% of mice will develop nonmammary epithelial tumors.
• This mouse model provides a valuable
tool to gain insights into the role
of E-cadherin loss of function in
mammary tumor initiation, progression,
and metastasis.
MODEL NUMBER 11509
CRYOP RES ERVED
Brca1-Associated
Breast Cancer Model
BREAST CANCER MODEL
• Conditional mouse mutant with
somatic deletion of Brca1 and Trp53
in several epithelial tissues including
mammary epithelium. Female mice
of this strain show a high incidence of
mammary tumors that mimic many
aspects of human BRCA1-mutated
basal-like breast cancer.
• Contains conditional disruption of
the Trp53 tumor suppressor gene,
the most commonly mutated gene
in human cancers.
• Contains conditional disruption of the
Brca1 gene. Germline mutations of this
gene are responsible for 40% to 50% of
hereditary breast cancers.
• This model may be helpful in predicting
responses of human BRCA1-deficient
tumors to therapies.
N OMENCLATURE
STOCK Trp53tm1Brn Brca1tm1Brn
Tg(KRT14-cre)8Brn
• Can be used to supply tumor tissues
for allografts.
• 20-30% of mice will develop nonmammary epithelial tumors.
• From the literature, it is estimated
that 80% of females develop multiple
mammary and skin epithelial tumors
with onset between 140 and 280 days.
MODEL NUMBER 11510
CRYOP RES ERVED
DISCUSS YOUR NEEDS
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Oncology | 16
ONCOLOGY
TACONIC BIOSCIENCES
Floxed Ink4a/Arf Mouse
CONDITIONAL TUMOR SUPPRESSOR ALLELE
• Contains a targeted mutation of
Cdkn2a (Ink4a/Arf) which introduced
LoxP sites upstream of exon 2 and
downstream of exon 3.
• Cross with the tissue-specific cre of
your choice to develop a tumor model.
N OM EN CLATURE
B6.129P2-Cdkn2atm2Brn/A
• The cell cycle inhibitory protein Cdkn2a
is frequently disrupted in various
types of human cancer, and germline
mutations of this locus can confer
susceptibility to melanoma and
other tumors.
• After deletion of the gene via crossing
to a tissue-specific cre line, mice can
develop tumors, giving rise to various
sarcomas, carcinomas, lymphomas, and
metastatic melanoma.
MODEL NUMBER 11511
C RYO P RES ERV ED
Floxed p53 Mouse
N OM EN CLATURE
CONDITIONAL TUMOR SUPPRESSOR ALLELE
B6.129P2-Trp53tm1Brn/A
• Contains a targeted mutation of Trp53
which introduced LoxP sites flanking
exons 2 through 10.
• Useful for studying Trp53 gene
function or screening potential cancer
intervention therapies.
• Cross with the tissue-specific cre of
your choice to generate a conditional
disruption of the Trp53 tumor
suppressor gene, the most commonly
mutated gene in human cancers.
• Conditional mutation avoids the
predominance of non-epithelial
tumors observed in constitutive
Trp53 knockouts.
• After deletion of the gene via
crossing to a tissue-specific cre line,
the incidence and the spectrum of
tumors observed in homozygous
or heterozygous mutant animals
were comparable to those found in
constitutive knockouts.
MODEL NUMBER 11512
C RYO P RES ERV ED
TO ORDER
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ONCOLOGY
TACONIC BIOSCIENCES
S PO NTANE O U S
T UM OR MO DEL S
Pirc
N OMENCLATURE
COLON CANCER MODEL
• Excellent model for study of human
familial colon cancer.
• ENU-induced point mutation results in
a truncating mutation in the Apc gene
at a site corresponding to the human
mutation hotspot region of the gene.
F344/NTac-Apcam1137
• Heterozygotes develop multiple tumors
in the small intestine and colon by 2-4
months of age.
• Pirc tumors closely resemble those in
humans in terms of histopathology,
morphology, and distribution between
intestine and colon.
• Longer lifespan compared to related
mouse models (12-15 months).
• Tumors may be visualized by CT,
endoscopy or dissection.
• Available for immediate cryorecovery.
MODEL NUMBER PIRC
CRYOP RES ERVED
Stat 1
N OMENCLATURE
MAMMARY TUMOR MODEL
• Contains a homozygous disruption of
the Stat1 gene and complete lack of
functional STAT1 proteins.
• The JAK-STAT signaling pathway has
been implicated in mediating biologic
responses induced by many cytokines.
129S6/SvEv-Stat1tm1Rds
• Deficient immune cell response to
alpha and gamma interferons.
• Accelerated and amplified
development of chemically-induced
and spontaneous tumors.
• Useful in unraveling the role of a variety
of cytokines in immune responses,
the role of STAT1 protein in mediating
interferon-dependent responses,
and the roles of tumor cells and
immune cells in mediating tumor
cell destruction.
MODEL NUMBER 2045
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Oncology | 18
ONCOLOGY
TACONIC BIOSCIENCES
TSG-p53®
N OM EN CLATURE
TUMOR SUPPRESSOR KNOCK OUT
• Contains a disruption of the Trp53
tumor suppressor gene, the most
commonly mutated gene in
human cancers.
• Useful for studying Trp53 gene
function or screening potential cancer
intervention therapies.
B6.129-Trp53tm1Brd N12
• Homozygous TSG-p53®
mice are totally deficient in p53
protein and prone to the development
of spontaneous tumors, primarily
lymphomas and sarcomas.
• Heterozygous TSG-p53® mice carry
one normal p53 allele and have a
much lower rate of spontaneous
tumor development.
MODEL NUMBER P53N12
C RYO P RES ERV ED
TO ORDER
19 | Oncology
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ONCOLOGY
TACONIC BIOSCIENCES
COMPARISON OF ONCOLOGY MOUSE AND RAT MODELS
MODEL NUMBER
MODEL NAME
COAT COLOR
T, B & NK CELL DEFICIENCIES
BALBNU
BALB/c nude
mouse
B6NU
B6 nude mouse
NCRNU
NCr nude mouse
NMRINU
NMRI nude mouse
NIHRNU
NIH nude rat
9066*
HRN™ nude mouse
1147
Jh
CB17SC
C.B-17 scid mouse
ICRSC
ICR scid mouse
NODSC
NOD scid mouse
RAG2
Rag2 (129S6)
mouse
461
Rag2 (B6.SJL)
mouse
601
Rag2 (BALB/c)
mouse
RAGN12
Rag2 (C57BL/6)
mouse
CBSCBG
Scid-beige mouse
4111
Rag2/Il2rg Double
Knockout Mouse
Dysfunctional antigen presenting cells (e.g. dendritic
cells and macrophages).
11503
CIEA BRG mouse
Dysfunctional antigen presenting cells (e.g. dendritic
cells and macrophages).
NOG
CIEA NOG mouse®
13395
NOG-EXL (hGMCSF/hIL-3 NOG)
13440
hIL-2 NOG
13686
hIL-6 NOG
13683
hIL-15 NOG
Shows reduced
NK function
OTHER IMMUNODEFICIENCIES
Dysfunctional antigen presenting cells (e.g. dendritic
cells and macrophages).
Reduced complement activity, dysfunctional
macrophages and dendritic cells. The most immune
deficient mouse available.
KEY:
COAT COLOR
CELL DEFICIENCIES
Black and
White Nude
White-bellied
agouti
T Cell Deficient
Black Nude
Black
B Cell Deficient
Albino Nude
Albino
NK Cell Deficient
* Lacks P450 activity in liver
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Oncology | 20
ONCOLOGY
TACONIC BIOSCIENCES
INTEGRATED CUSTOM
MODEL GENERATION
CUSTOM MODEL
GENERATION SOLUTIONS
Taconic’s Genetically Engineered Models
(GEMs) Design Solutions empower our
clients to develop research models
specifically suited to the unique discovery
study needs or therapeutic programs. As a
market leader with decades of experience
in custom model generation, Taconic
partners with clients to design, develop,
and breed high quality genetically
engineered mouse and rat models.
GENE FUNCTION STUDIES
GENE
INACTIVATION
DISEASE MODELING:
MECHANISM OF PATHOGENESIS
TRANSGENE
EXPRESSION
DISEASE MODELING:
DRUG TESTING & DEVELOPMENT
INDUCIBLE/
REVERSIBLE CONTROL
OF GENE FUNCTION
Constitutive
knock out
Targeted
Transgenesis
Conditional
knock out
Conditional
Targeted Transgenesis
Inducible/reversible
RNA interference
Conditional
knock out with
Cre-ER gene switch
Random
Transgenesis
Inducible/reversible
miRNA overexpression
Constitutive with
the option for
conditional
knock out
GENE MUTATION
OR REPLACEMENT
Constitutive knock in
Human gene knock in
Human gene knock in
with optional conditional
knock out
Conditional knock in
Constitutive knock in
point mutation with
conditional knock out
CRISPR Gene Editing
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ONCOLOGY
TACONIC BIOSCIENCES
INTEGRATED CUSTOM
BREEDING SOLUTIONS
TACONIC OFFERS A SUITE OF PROJECT MANAGEMENT SERVICES
TO HELP DRIVE NEW ONCOLOGY MODEL DEVELOPMENT
FORWARD WITH INDUSTRY LEADING QUALITY AND SPEED.
CUSTOM BREEDING SOLUTIONS
Taconic’s fully integrated custom
breeding solutions help bring novel
oncology models from concept to
study-ready cohorts with unprecedented
speed and transparency. Customers
can also combine Taconic’s portfolio
of spontaneous and conditional tumor
models with their existing or newly
generated lines to delve into new frontiers.
Our internal teams are led by PhDscientists trained in project management
principles to balance speed, cost, and
quality in order to meet your customized
project goals. Custom Breeding Solutions
coordinates flexible tools and advanced
technologies, including:
• Embryology
Complete
Portfolio
and Project
Management
Access to
Subject Matter
Expertise
• Animal housing
• Molecular analysis
• Surgery and specimen collection
• Shipping animals with choice
of animal identification system
pre-applied
Flexibility in
Capabilities
and Service
Offerings
Global
E-Business
Suite and
Electronic
Offerings
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Oncology | 22
ONCOLOGY
Take Your Research Further
GEMs DESIGN
PRECISION RESEARCH MODELS
GEMs MANAGEMENT
Taconic Biosciences Genetically
Engineered Models (GEMs) Design
empowers our clients to develop research
models specifically suited to the unique
needs of their discovery and development
studies or therapeutic programs.
Research organizations demand
precision tools that better reflect human
physiology. Taconic Biosciences leads
the field delivering innovative solutions
to meet these continually evolving
needs. Our core competencies include
the delivery of complex strategies that
both integrate human genetic sequences
and engraft human cells and tissues into
custom mouse and rat models.
Taconic’s fully integrated GEMs
Management brings innovative models
from design to study-ready cohorts with
unprecedented speed and transparency.
• Human Gene Replacement
• Genotyping and Molecular Analysis
• Gene Inactivation
• Gene Mutation or Replacement
• CRISPR Gene Editing
• Transgene Expression
• miRNA Expression
• Cohort Production Packages
• Human Cell and Tissue Engraftment
•Embryology
• Rapid Colony Expansion
• Contract Breeding
• Surgical Services
• Tissue Collection
• Microbiome and Germ-Free Research
Models and Services
CHOOSE TACONIC
TALK TO A SCIENTIST
For more than 60 years, Taconic has anticipated
the needs of the scientific community to deliver
models and services that meet the diverse needs of
biomedical and biopharmaceutical researchers.
Our scientific teams are happy to meet and talk
with you about the most efficient way to achieve
your study goals. Working in partnership with
clients the world over, our scientific teams offer
expert advice that can help you speed up your
research and reduce your overall costs.
Today that forward thinking and commitment to
working collaboratively has resulted in a client-centric
environment infused with a knowledge bank that
allows you to select the optimum model for your
study based on informed insight into the generation
of genetically engineered mouse and rat models.
YOUR COLLABORATIVE PARTNER
As a full-service biosciences company, Taconic can help
you acquire, test, develop, breed, cryopreserve, prepare,
and distribute highly relevant research lines worldwide.
Whether you require custom genetically engineered,
cell or tissue engrafted models or traditional models,
Taconic’s scientists will partner with you to rapidly
and efficiently deliver the highest quality models.
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TACONIC.COM
©Taconic Biosciences, Inc. All rights reserved. Contents of this publication
may not be reproduced in any form without prior permission.
BR1037-EN-1703
TALK TO A REPRESENTATIVE
For general information, you can talk to a member
of our customer service team. Our customer
service team is here to help you make the right
decisions and get the models you need fast.
Contact us at [email protected]
VISIT TACONIC.COM
For more information on the entire Taconic
portfolio of products and services designed to
help further your research, visit taconic.com