Improve Fc-engineered antibody ranking

Make confident preclinical decisions when Fc‑mediated efficacy and toxicity must be balanced

Optimizing the Fc region of a therapeutic antibody is critical but risky. Enhancing Fc‑mediated immune activation can unlock powerful efficacy, yet even small missteps can lead to excessive immune activation, toxicity, or poor clinical translation.

‍

The challenge:

‍How do you evaluate Fc‑engineered antibodies in preclinical studies and confidently select the best candidate using data that reflects human immune biology?

The limits of conventional mouse models

Standard mouse models often fail to accurately represent human Fcγ receptor biology, making it difficult to:

• Predict Fc‑mediated immune responses in humans
• Compare and rank Fc variants with confidence
• Balance efficacy with safety early in development

‍

As a result, Fc optimization decisions are frequently made with incomplete or poorly translatable data, increasing downstream risk.

The solution:‍

genOway’s humanized FcγR (genO-hFcγR) mouse model, which enable a more human‑relevant approach to Fc assessment.

By incorporating human Fcγ receptor biology into preclinical mouse models, genO-hFcγR mice enable a more translatable evaluation of Fc‑mediated immune activation, supporting better antibody ranking and safer candidate selection before entering the clinic.

‍

Guide: Compare FcγR mouse models and select the most relevant platform for evaluating therapeutic antibodies and Fc-mediated mechanisms. Read the guide →

‍

‍

The genO-FcγR model has been validated by leaders in the field, who demonstrated:

‍

• ‍Human‑like FcγR expression and distribution
  The model includes humanized FcγRI, FcγRIIA, FcγRIIB, FcγRIIIA, and FcγRIIIB, expressed in a pattern closely aligned with human biology (Van Damme KFA et al., Sci. Immunol., 2026)‍

‍

‍‍

• ‍Proven ability to rank antibodies in vivo
  Demonstrated use of the genO-hFcγR mouse model to discriminate Fc variants and support antibody ranking decisions (Van Damme KFA et al., Sci. Immunol., 2026)

‍

‍

• ‍Valuable tool for testing cell-depleting antibodies

            An anti-CD20 antibody depleted B cells in the humanized genO-hFcγR model, while its silenced Fc variant did not. Similar data was presented at different conferences by us and argenx

‍

‍

Portfolio of humanized FcγR models

In order to expand the range of applications of our genO-hFcγR mouse, it has been crossed with several other models:

‍

‍

‍

‍

List of references

‍
Scientific papers:

• Stefanutti et al., "Analysis of Fc-dependent effector functions of anti-malaria circumsporozoite protein antibodies" - Fcγr Humanized Knockin | Publication | genOway
• Van Damme et al., "Cross-species cellular mapping and humanization of Fcγ receptors to advance antibody modeling" - Fcgr1, Fcgr2a, Fcgr2b, Fcgr3a, Fcgr3b, Fcgrt Replacement of murine Fcgr loci by human FcγR genes | Publication | genOway

‍

Posters:

• Sônego et al., 2023, SITC, "Cell-depleting agents assessment in preclinical models" - Cell-depleting agents assessment in preclinical models | Poster | genOway
• Van Damme et al., 2023, EMDS, "A Cross-Species Map and Humanized Mouse Model of Fcγ Receptors and FcRn" - Humanized Mouse Model of Fcγ Receptors | Poster | genOway
• Sônego et al., 2024, AACR, "Novel FcγR humanized mouse models enabling efficacy and PK/PD of therapeutic antibodies" - FcγR humanized mouse models for efficacy and PK/PD of therapeutics | Poster | genOway
• Pappalardo et al., 2026, AACR, "Humanized FcγR/FcRn mouse model exhibits immunological responses comparable to wild-type mice" - Humanized FcγR/FcRn Mouse Model | Poster | genOway
  ‍