FcResolv® NOG Portfolio

Super immunodeficient mouse models with murine Fc gamma receptors knocked out provide improved accuracy in antibody-based studies.

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.

Connect with an expert
black mouse

Improve your antibody-based therapy assessment in three critical ways:

 

Greater Confidence in Your Study Results

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

More Accurate Assessment of Antibody-Based Therapies

Distinguish true drug efficacy from off-target effects mediated through the mouse immune system and eliminate costly deconvolution steps.

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 provides improved clarity for more reliable answers.

FcResolv® NOG Portfolio

FcResolv® NOG mouse models expand the utility of the powerful Taconic NOG platform. They are ideal for investigating any indication which utilizes a therapy incorporating an Fc domain, including immuno-oncology, autoimmune disease, and more.

FcResolv® NOG Models

  • Reduced residual murine immune activity due to functional knockout of mouse FcγRs
  • Suitable for tumor xenografts using cell lines or patient-derived tumors
  • Ideal for engraftment of normal or pathological human cells and tissues, and immune system humanization studies

Available options:

  • Transgenic expression of hIL-15 cytokine to support engraftment of human NK cells
  • Transgenic expression of hGM-CSF/hIL-3 (NOG-EXL background) to support human myeloid cell reconstitution
  • Humanized immune system (HIS) model engrafted with human CD34+ HSC

NOW AVAILABLE! FcResolv® NOG-EXL models

Combined benefits from two validated mouse models for superior results

  • Prevent Fc gamma receptor interference that leads to false positives or false negatives
  • Enable consistent human myeloid cell reconstitution
  • Ideal for antibody-based therapeutics with potential for Fc domain interference
  • Available as HIS model engrafted with CD34+ HSC

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.

chart of absent receptors in 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.

nog permits detection antibody based immunotherapy efficiency graphics

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.

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 diagram

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.

specifically detect diagram

FcResolv NOG Model: FAQs

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. The FcResolv NOG-EXL is suited for studies requiring myeloid or lymphoid cell reconstitution, with particular utility for studying acute myelogenous leukemia (AML).

Get In Touch

Book a complimentary consultation or get support for an existing order

If you need immediate assistance, please contact Customer Service:

Taconic Corporate Offices

Email: info@taconic.com
Phone: +1 (518) 697-3900
273 Hover Ave., Germantown, NY 12526

North American Customer Service

Email: info@taconic.com
Phone: +1 (518) 697-3915 
Toll-free:  +1 (888) 822-6642

Hours: (Monday - Friday): 7 a.m. - 6 p.m. ET

European Customer Service

Email: info@taconic.com
Phone (Europe and Denmark): +45 70 23 04 05 
Phone (Germany): +49 214 50 68 023 
Hours: (Monday - Friday): 7 a.m. - 5 p.m. CET

Let's Get Social!

How can we help you?
Fill out the form to connect with us:

Welcome! Tell us a little about yourself