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.

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.

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.

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-Ptprca	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.

*Available from Taconic's cryopreserved repository.

Transgenic HLA Mice for Syngeneic Tumor Models

HLA CLASS I
MODEL	STRAIN BACKGROUND	DESCRIPTION	MGI
HLA-A2.1	C57BL/6 or CB6F1	Expresses the chimeric HLA-A2.1 class I molecule (representing the HLA-A2 supertype) on the surface of T and B cells.	Link
HLA-A11	C57BL/6 or CB6F1	Expresses the chimeric HLA-A11 class I molecule (representing the HLA-A3 supertype) on the surface of T and B cells.	Link
HLA-A1	C57BL/6 or CB6F1	Expresses the chimeric HLA-A1 class I molecule (representing the HLA-A1 supertype) on the surface of T and B cells.	Link
HLA-A24	C57BL/6 or CB6F1	Expresses the chimeric HLA-A24 class I molecule (representing the HLA-A24 supertype) on the surface of T and B cells.	Link
HLA-B7	C57BL/6 or CB6F1	Expresses the chimeric HLA-B7 class I molecule (representing the HLA-B7 supertype) on the surface of T and B cells.	Link
HLA-B44	C57BL/6 or CB6F1	Expresses the chimeric HLA-B44 class I molecule (representing the HLA-B44 supertype) on the surface of T and B cells.	Link
HLA CLASS II
Abb Knockout/ Transgenic HLA-DR4	C57BL/6	Expresses the chimeric HLA-DR4 class II molecule on the surface of T and B cells.	Link

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.

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