SYNGENEIC TUMOR MOUSE MODELS

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Syngeneic Tumor Mouse Models & Research Tools Overview

Syngeneic tumor models are widely used for immuno-oncology because they offer an in vivo system with normal immune function for testing immune-modulating therapeutics. To generate a syngeneic tumor model, tumor cells derived from a particular inbred strain are engrafted into hosts of the same strain. Syngeneic tumor models are relatively easy to generate and inexpensive. They are often used for large-scale screening, but differences between human and mouse tumors and immune cells may reduce their predictive ability.

Taconic Biosciences offers a range of syngeneic tumor hosts from simple inbred strains through sophisticated genetically engineered models (GEMs). Taconic does not offer study services, but our experts can provide guidance on study design and selection of the most appropriate animal model as well as referrals to qualified contract research organizations.

generation of syngeneic tumor models
Tumor originating
in an inbred strain
Tumor cell line
Grown in vitro
Tumor cells implanted in
mice of same inbred strain

ADVANTAGES OF SYNGENEIC MOUSE MODELS FOR IMMUNO-ONCOLOGY RESEARCH

Fully intact immune system

Tumor, immune system, and stroma are genetically matched

Compatible with existing and custom GEMs enabling greater flexibility

Germ-free and gnotobiotic inbred strains available for microbiome studies

Genetically engineered Jh Mouse enables researchers to conduct syngeneic studies without the negative effects of immunogenicity

STANDARD INBRED STRAIN USED AS HOSTS FOR SYNGENEIC TUMOR EXPERIMENTS

Taconic offers key inbred strains at multiple health standards, including Germ Free, to facilitate oncology studies with a microbiome component.

STRAIN TACONIC MODELS
NOTES
C57BL/6 C57BL/6NTac Th1 immune bias. B6 and BALB/c are the two most commonly used strain backgrounds for syngeneic tumor studies.
C57BL/6JBomTac
BALB/c BALB/cAnNTac Th2 immune bias. B6 and BALB/c are the two most commonly used strain backgrounds for syngeneic tumor studies.
BALB/cJBomTac
C3H C3H/HeNTac
DBA/2 DBA/2NTac
FVB FVB/NTac Primarily used for mammary tumor studies.
DBA/1 DBA/1JBomTac
129S6 C3H/HeNTac

Taconic has compiled a database of published syngeneic tumor cell lines, with details on cancer type, strain background, immunogenicity and metastatic potential. Filter or search by any of these characteristics to identify relevant cell lines for your research.

The Jh MOUSE

Antibody-deficient C57BL/6 and BALB/c mice for immuno-oncology research.

The Jh Mouse permits clinically-relevant dosing of immunogenic test articles in syngeneic tumor model systems.

Standard Inbred Strain

BALB/c mouse
Implemented with syngeneic tumor cell line derived from BALB/c or

C57BL/6 mouse
Implanted with syngeneic tumor cell derived from C57BL/6

Standard inbred host develops humoral immune response (anti-drug antibodies) against test article, which can neutralize the therapy or even cause anaphylaxis.

Jh Mouse

Jh Mouse implanted with syngeneic tumor cell line derived from BALB/c or C57BL/6

Taconic offers two Jh models:

The Jh Mouse lacks B cells, so no anti-drug antibodies are produced. It retains other immune cell types such as T cells, so immunotherapies can be successfully evaluated using clinically-relevant dosing.

The Jh Mouse may be crossbred to other GEM strains, such as genetically humanized PD-1 mice to further extend the utility of this system. Inquire for details on crossbreeding rights.

C57BL/6 suite of strains for syngeneic tumor modeling

STRAIN STRAIN TYPE IMMUNODEFICIENCIES NOTES
C57BL/6NTac Inbred None Inbred strain. B6/N substrain. Widely available in North America and Europe.
C57BL/6JBomTac Inbred None Inbred strain. B6/J substrain. Widely available in Europe.
B6.SJL-Ptprc Adoptive Transfer None Congenic on C57BL/6NTac. Carries the SJL-derived Ptprca (Cd45.1/Ly5.1) allele, which can be used to distinguish between transferred lymphocytes derived from this donor strain and C57BL/6NTac recipient mice.
β-actin-luc Adoptive Transfer None Reporter strain with constitutive expression of luciferase in all tissues tested. May be used as source of luciferase-labeled donor cells for adoptive transfer into C57BL/6 recipient mice.
Rag2/OT-I TCR Transgenic Does not develop mature T or B cells expressing endogenous T cell receptors. Useful as either a tumor recipient or as a source of homogenous donor CD8+ T cells for in vivo adoptive transfer studies to investigate MHC class I-restricted CD8+ T cell responses to ovalbumin-expressing tumors.
Rag2/OT-II TCR Transgenic Does not develop mature T or B cells expressing endogenous T cell receptors. Useful as either a tumor recipient or as a source of homogenous donor CD4+ T cells for in vivo adoptive transfer studies to investigate MHC class II-restricted CD4+ T cell responses to ovalbumin-expressing tumors.
Jh (C57BL/6) Immunodeficient Lacks B cells B cell-deficient but retains other immune cell types such as T cells and myeloid cell populations. Useful for studying immunotherapies that could induce ADA and/or anaphylaxis in wild type mice.
Rag2 Knockout Immunodeficient Lacks T and B cells Tumors may grow more quickly in an immunodeficient host. Amenable to adoptive transfer of immune cells from C57BL/6NTac or other C57BL/6 lines.
Rag2/Il2rg Knockout Immunodeficient Lacks T, B and NK cells; dysfunctional dendritic cells. Tumors may grow more quickly in an immunodeficient host. Amenable to adoptive transfer of immune cells from C57BL/6NTac or other C57BL/6 lines.
Abb Knockout
Immunodeficient Expresses no A or E MHC class II molecules and therefore lacks most CD4+ T cells. Useful for mechanistic studies of the immune response by eliminating CD4+ T cell responses.
Abb Knockout with Ptprca Immunodeficient Expresses no A or E MHC class II molecules and therefore lacks most CD4+ T cells. Useful for mechanistic studies of the immune response by eliminating CD4+ T cell responses. Carries the SJL-derived Ptprca (Cd45.1/Ly5.1) allele, which can be used to distinguish between transferred lymphocytes derived from this donor strain and C57BL/6NTac recipient mice and vice versa.
B2m Knockout* Immunodeficient Deficient in MHC Class I molecule expression and exhibits depletion of CD8+ and NK1.1+ CD4+ T cells. Useful for mechanistic studies of the immune response by eliminating CD8+ T cell responses. Note: may also show decreased immunoglobulin half life in this model due to decreased FcRn expression.
Abb/B2m Knockout* Immunodeficient Expresses no A or E MHC class II molecules and therefore lacks most CD4+ T cells. Deficient in MHC Class I molecule expression and exhibits depletion of CD8+ and NK1.1+ CD4+ T cells. Useful for mechanistic studies of the immune response by eliminating both MHC class I and II signaling.
Fcer1g (FcRγ) Immunodeficient Deficient in the gamma chain subunit of the FcgRI, FcgRIII and FceRI receptors, resulting in functionally impaired macrophages, neutrophils, mast cells, basophils and NK cells. Useful for studies to distinguish the role of the Fc receptors in antibody-mediated effector responses and to evaluate the contribution of IgG and IgE triggered effector pathways.
Fcgr2b (FcyRII) Immunodeficient Deficient in FcgRIIB protein, a low affinity immunoglobulin G receptor which inhibits the activation of disparate effector functions such as phagocytosis, antibody dependent cytotoxicity and release of inflammatory mediators. Useful in mechanistic studies by removing the inhibitory function of FcgRIIB, or in identifying antibody-mediated FcgRIIB-dependent crosslinking effector mechanisms.
HLA-A2.1 Transgenic HLA Mice None May be useful for cancer vaccine approaches. Expresses the chimeric HLA-A2.1 class I molecule (representing the HLA-A2 supertype) on the surface of T and B cells. CB6F1 background. C57BL/6 background available on request as model #8906.
HLA-A11 Transgenic HLA Mice None May be useful for cancer vaccine approaches. Expresses the chimeric HLA-A11 class I molecule (representing the HLA-A3 supertype) on the surface of T and B cells. CB6F1 background. C57BL/6 background available on request as model #8907.
HLA-A1 Transgenic HLA Mice None May be useful for cancer vaccine approaches. Expresses the chimeric HLA-A1 class I molecule (representing the HLA-A1 supertype) on the surface of T and B cells. CB6F1 background. C57BL/6 background available on request as model #8909.
HLA-A24 Transgenic HLA Mice None May be useful for cancer vaccine approaches. Expresses the chimeric HLA-A24 class I molecule (representing the HLA-A24 supertype) on the surface of T and B cells. CB6F1 background. C57BL/6 background available on request as model #8910.
HLA-B7 Transgenic HLA Mice None in CB6F1 background; C57BL/6 background may have deficiencies in murine MHC class I expression. May be useful for cancer vaccine approaches. Expresses the chimeric HLA-B7 class I molecule (representing the HLA-B7 supertype) on the surface of T and B cells. CB6F1 background. C57BL/6 background available on request as model #8908.
HLA-B44 Transgenic HLA Mice None May be useful for cancer vaccine approaches. Expresses the chimeric HLA-B44 class I molecule (representing the HLA-B44 supertype) on the surface of T and B cells. CB6F1 background. C57BL/6 background available on request as model #8911.
Abb Knockout/Transgenic HLA-DR4 Transgenic HLA Mice Deficient in endogenous murine MHC Class II. May be useful for cancer vaccine approaches. Expresses the chimeric HLA-DR4 class II molecule on the surface of T and B cells.
*Available from Taconic's cryopreserved repository.

Note: Syngeneic tumor take rate and growth kinetics may vary between wild type and immunodeficient mice on the same strain background. A pilot study is always good practice to assess cell line choice and experimental conditions prior to a full study.

Balb/c suite of strains for syngeneic tumor modeling

STRAIN STRAIN TYPE IMMUNODEFICIENCIES RELEVANCE TO SYNGENEIC STUDIES
BALB/cAnNTac Inbred None Inbred strain.
BALB/cJBomTac Inbred None Inbred strain.
Jh (BALB/c)  Immunodeficient Lacks B cells B cell-deficient but retains other immune cell types such as T cells and myeloid cell populations. Useful for studying immunotherapies that could induce ADA and/or anaphylaxis in wild type mice.
Fcer1g (FcRγ) Immunodeficient Deficient in the gamma chain subunit of the FcgRI, FcgRIII, and FceRI receptors. Macrophages, neutrophils, mast cells, basophils, and NK cells are functionally impaired, due to the lack of these Fc receptors. Useful in determining the role of structurally similar Fc receptors in mediating effector immune responses and studying the pleiotropic role of the g chain subunit.
Fcgr2b (FcγRII) Immunodeficient Deficient in the FcgRIIB protein, resulting in the inability to regulate antibody levels in response to antigenic stimuli dependent on IgG immune complexes. Useful in mechanistic studies by removing the inhibitory function of FcgRIIB, or in identifying antibody-mediated FcgRIIB-dependent crosslinking effector mechanisms.
Rag2 Knockout Immunodeficient Lacks T and B cells Congenic on BALB/cAnNTac. Tumors may grow more quickly in an immunodeficient host. Amenable to adoptive transfer of immune cells from BALB/cAnNTac or other BALB/c lines.
Rag2/Il2rg Knockout (BRG) Immunodeficient Lacks T, B and NK cells; dysfunctional dendritic cells. Congenic on BALB/c. Tumors may grow more quickly in an immunodeficient host. Amenable to adoptive transfer of immune cells from BALB/c lines.
NFκB-RE-luc Reporter Lacks T and B cells Potentially useful in imaging host immune responses to syngeneic tumors in vivo.
Note: Syngeneic tumor take rate and growth kinetics may vary between wild type and immunodeficient mice on the same strain background. A pilot study is always good practice to assess cell line choice and experimental conditions prior to a full study.

ARE YOU READY TO START YOUR SYNGENEIC STUDY?

Ready to conduct syngeneic study

CUSTOM SOLUTIONS FOR ONCOLOGY AND IMMUNO-ONCOLOGY RESEARCH

Taconic Biosciences' globally-recognized scientific project managers support your custom model design project from design to delivery. Each custom model design project develops along an agile framework, letting you reassess and retarget your model fluidly as new data becomes available. You can pause or postpone projects at any time, or even "back up" project milestones via cryopreservation.

Model Generation Solutions
& Breeding Services

  • Model Acquisition
  • Transition Mutant to Model
  • Scaled Breeding
  • Specialized Services
  • Distribution

Colony Management Solutions

  • Extensive Health Standard Options
  • True Gnotobiotic Profiles
  • Genetic Monitoring Programs
  • Scientific Leadership & Success Team
  • Custom Solutions for Every Partner

Syngeneic cell lines derived from cancer GEMS

Syngeneic tumor cell lines are most commonly derived from wild type inbred strains, but cancer GEM models can also be used. Cancer GEMs are models in which particular mutations have been introduced to provoke spontaneous tumor development. These models are often designed such that they carry mutations found in particular human cancer types. Taconic offers several spontaneous tumor models.

Comparing syngeneic tumor models and humanized immune system mice

When it comes to immuno-oncology, the two most common preclinical systems are syngeneic tumor models and humanized immune system mice implanted with a human cell line or patient-derived xenograft. Learn more about the pros and cons of each approach:

SYNGENEIC MODELS VERSUES HUMANIZED IMMUNE SYSTEM (HIS) MICE

Syngeneic

Tumor

Host

  • Fully-intact immune system
  • Tumor genetically matched with immune system and stroma
  • Mouse vs. human differences

Humanized

Tumor Immune Cells Host
  • Human tumor with human immune cells
  • Limitations on immune cell engraftment
  • Potential for graft vs. host disease (GvHD)
  • Species mismatch between tumor/immune cells and stroma
Model Type Syngeneic Models Humanized Immune System (HIS) Models
Benefits
  • Complete and intact immune system
  • Tumor, immune system and stroma are genetically matched
  • Flexibility
  • Host strains are inexpensive and available in large quantities
  • Compatibility with existing and current GEMs enabling greater flexibility and mechanistic insight
  • Availability of germ-free and gnotobiotic inbred strains for microbiome studies
  • Ability to use clinical candidate directly
  • Potential for greater translatability by studying human tumors and human immune cells
  • Compatible with patient-derived xenografts (PDX)
  • Readily available with pre-engrafted options such as huNOG and huNOG-EXL
Challenges
  • Availability of well-characterized cell lines for some tumor types (e.g., lung cancer)
  • Translatability of mouse tumors to patients and lack of patient-derived options
  • Species-specific differences between human and mouse immune systems
  • Potential requirement for using mouse surrogates for human-specific therapeutics (e.g. biologics)
  • Limited availability of GEMs on certain genetic backgrounds
  • Long timeframes for custom GEM generation
  • Limitations of immune cell engraftment and function
  • Choice of humanized immune system (HIS) model must be based on immune mechanism studied
  • Potential for GvHD in some HIS models
  • Not compatible with GEMs for mechanistic studies
  • Cost

Featured Resources for Syngeneic Tumor Studies

Video - The Jh Mouse Enables Syngeneic Studies with Immuno-Oncology Therapeutics

VIDEO

The Jh Mouse Permits Clinically-Relevant Dosing of Immunogenic Test Articles in Syngeneic Tumor Model Studies

Syngeneic Mouse Models for Preclinical Immuno-Oncology Research

WHITE PAPER

Syngeneic Mouse Models for Preclinical Immuno-Oncology Research

Syngeneic Cell Line Database

CELL LINE DATABASE

The Syngeneic Cell Line Reference Database can help identify tumor cell lines and associated background strains to select the most appropriate model for your study.

Advanced Toolkit For Syngeneic Tumor Modeling in Mice

ON-DEMAND WEBINAR

Advanced Toolkit For Syngeneic Tumor Modeling in Mice

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