FcResolv NOG Portfolio
For Antibody-Based Drug Studies

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The First and Only Super Immunodeficient Mouse Models that Remove Murine Fc Gamma Receptors Known to Confound Results

Researchers who work with antibody-based therapies find that murine Fc gamma receptors (FcγRs) can confound preclinical study results, causing false positives or false negatives that lead to incorrect conclusions and derail drug discovery. By knocking out these receptors, FcResolv™ NOG models provide clarity in antibody-based drug studies, offering greater confidence and more translatable data while utilizing fewer resources.

These novel mouse models improve your antibody-based therapy assessment in three critical ways:

Greater Confidence in Your Study Results

Eliminate the false negatives that occur when an antibody-based therapeutic's Fc domain interacts with murine FcγRs and the false positives that result when FcγRs trigger residual murine immune activity.

More Accurate Assessment of Antibody-Based Therapies

Eliminate costly deconvolution steps otherwise needed to distinguish true drug efficacy from off-target effects mediated through the mouse immune system. Gain clarity on your therapeutic's mechanism of action without interference from murine FcγR activity.

Better Answers with Fewer Resources

Avoid wasteful investments based on false positives or missing out on a promising candidate due to false negatives. FcResolv NOG mouse models can give you more reliable answers faster using fewer studies and animals.

WHICH FcResolv NOG MODEL IS RIGHT FOR YOUR STUDY?

FcResolv NOG mouse models expand the utility of Taconic's powerful NOG platform and can be used in similar applications as the base models (CIEA NOG mouse® and hIL-15 NOG). FcResolv NOG mice are ideal for investigating any indication which utilizes a therapy incorporating an Fc domain, including immuno-oncology, autoimmune disease, and more.

FcResolv NOG


Super immunodeficient NOG mouse

  • Reduces residual murine immune activity by functionally knocking out mouse FcγRs.
  • Suitable for similar applications as the CIEA NOG mouse®, including tumor xenografts using cell lines or patient-derived tumors, engraftment of other normal or pathological human cells and tissues, and immune system humanization studies.

FcResolv hIL-15 NOG


Super immunodeficient NOG mouse expressing human IL-15 cytokine to support engraftment of human NK cells

COMING SOON: FcResolv huNOG

Humanized immune system (HIS) mouse model based on the FcResolv NOG mouse

Supports long-term engraftment of human lymphoid cells

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SUPPORTING DATA

The FcResolv NOG model portfolio is based on the super immunodeficient NOG mouse. This highly versatile strain lacks adaptive immune cells and has an attenuated innate immune response, yet still retains some residual mouse immune cells that can interact with therapeutic antibodies. FcResolv NOG models eliminate this interaction by knocking out the activity of all murine FcγRs, including the FcγRI, IIB, III and IV types, along with the high affinity FcεRI receptor. The low affinity FcεRII receptor remains present.

Mouse Fc Receptors Absent in FcResolv NOG Models

Mouse Fc Receptors Absent in FcResolv NOG Models

Table of all Fc receptors whose function is knocked out in the FcResolv NOG mouse models, including their expression patterns and binding affinity of various mouse and human immunoglobulin G and E (IgG and IgE) subclasses. Note that FcεRI also requires the FcRγ common subunit and is nonfunctional in the FcResolv NOG model. The low affinity FcεRII receptor remains present.

FcResolv NOG Permits Accurate Detection of Antibody-based Immunotherapy Efficacy

FcResolv NOG Permits Accurate Detection of Antibody-based Immunotherapy Efficacy

Functional knockout of murine FcγR activity enables accurate detection of immunotherapy efficacy in humanized mice engrafted with tumors. Nivolumab (anti-PD1) does not suppress tumor growth in HSC-engrafted NOG mice (bottom row) but displays anti-tumor efficacy in HSC-engrafted FcResolv NOG mice (top row) where there are no murine FcγRs to interact with the Fc domain of the therapeutic. From Katano et al. 2021.



Alleviate False Positives Generated by Murine Innate Cell-Mediated ADCC or ADCP

Intact FcγRs are expressed on residual murine immune cells in super immunodeficient NOG mice. These murine FcγRs can interact with the Fc domain of an antibody-based therapeutic and trigger an effect (for example, tumor growth inhibition) that is mediated through mouse innate immune cells and is independent of the therapeutic's intended mode of action. In FcResolv NOG mice, these receptors are absent, so there is no mouse innate immune response to interfere with interpretation of an Fc-based antibody therapeutic's efficacy.

In super immunodeficient NOG mice, FcγRs are expressed on residual murine immune cells. Although the exact mechanisms are not yet well-understood, these innate mouse receptors can bind antibody-based therapeutics through recognition of the Fc domain and interfere with the therapeutic's intended activity. In FcResolv NOG mice these receptors are absent, so there is no opportunity for them to interfere with interpretation of an antibody therapeutic's efficacy.

Alleviate False Negatives

Specifically Detect Human NK Cell-Mediated ADCC

The hIL-15 NOG mouse supports human NK cell engraftment through expression of the human IL-15 cytokine and can be used to study therapeutics which act through ADCC mediated by human NK cells. However, FcγRs expressed on residual murine immune cells in the hIL-15 NOG mouse can interact with the Fc domain of an antibody-based therapeutic and trigger off-target effects (for example, tumor growth inhibition) mediated through mouse innate immune cells which are independent of the therapeutic's intended mode of action. In FcResolv hIL-15 NOG mice these FcγRs are absent, so human NK cell-mediated ADCC can be specifically detected without having to deconvolute the contribution of off-target effects to observed efficacy.

Contact Taconic to learn how the FcResolv NOG or FcResolv hIL-15 NOG can help you obtain the right answers, faster and with greater confidence, when evaluating antibody-based therapies.

FREQUENTLY ASKED QUESTIONS (FAQs) ABOUT FcResolv NOG MODELS

To prevent expression of several different Fc receptors, two genes are knocked out in the FcResolv NOG models: the Fcgr2b gene, which encodes for FcγRIIb, and the Fcer1g gene, which encodes for the common FcRγ subunit. This approach prevents cell surface expression of FcγRI, FcγRIII, FcγRIV, and FcεRI. See our Fc receptor data table for more details.
The most well-understood mechanism through which Fc receptors confound antibody-based therapy studies occurs when an Fc domain interacts with those receptors, which then activate murine innate cells to cause xenograft tumor killing via ADCC or antibody-dependent cellular phagocytosis (ADCP). This mechanism and other possible sources of confounding factors are illustrated above.
Any antibody-based therapy that includes an Fc domain may benefit from study in an FcResolv NOG mouse, as it reduces confounding effects introduced by the drug's interaction with mouse Fc receptors. Suitable applications for the FcResolv NOG model portfolio include studies on monoclonal antibodies (mAbs), bispecific and trispecific antibodies, bispecific T cell engagers (BiTEs), bispecific killer cell engagers (BiKEs), trispecific killer cell engagers (TriKEs), NK cell engagers (NKCEs) and dual affinity retargeting antibodies (DARTs), along with other forms of engineered antibody scaffolds.
FcResolv NOG mouse models are versatile, super immunodeficient models that lend themselves to a wide variety of therapeutic areas, including immuno-oncology, autoimmune disease, infectious disease, regenerative medicine, and more. The FcResolv hIL-15 NOG is most useful for studies involving human NK cells, primarily related to immuno-oncology.

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