Ready to Move Beyond the Limitations of Your TCE Model for Efficacy Studies?

Testing T cell engagers (TCEs) for immuno-oncology can be difficult when preclinical models fail to reflect human target expression, T cell activation, and tumor immune evasion mechanisms such as inhibitory checkpoints and immunosuppressive cells. Oversimplified mouse models, surrogate constructs, and PBMC reconstituted systems often overestimate efficacy and fail to predict clinical behavior.

‍

Which Pre-Clinical Model is Right for Your TCE Efficacy Testing?

Whether you're developing bispecifics, trispecifics, Fc engineered molecules, or costimulatory CD28-based TCEs, genOway provides human relevant mouse models validated with biopharma partners and TAA-expressing cell lines that help you generate more predictive efficacy data:

‍

hCD3 models:

‍

genOway’s portfolio of hCD3 models has been used by biopharma companies like AstraZeneca and Pfizer to reliably assess their T-cell engagers. This is thanks to the following features:

Physiological human CD3 expression
Unaltered CD3/TCR interactions
Functional T/B cell cooperation and immune homeostasis

‍

These features ensure your TCE engages its target like it would in humans, delivering more reliable efficacy predictions.

‍

Examples of pharmaceutical companies that have used genOway’s hCD3 models

Pfizer evaluated PF07260437, a B7-H4×CD3 bispecific that redirects T cells to kill B7-H4⁺ breast cancer cells, using the genO-hCD3ε model

Graph of tumor volume over time showing improved tumor growth inhibition with combined PF‑07260437 and anti‑PD‑1 treatment compared with vehicle or single agents. — **Figure 1 –** Tumor growth inhibition of E0771 cells expressing B7-H4 implanted in genO-hCD3ε mice. Mice were treated with PF-07260437 alone, or in combination with a murine anti-PD-1. Treatment with the TCE alone or in combination leads to efficient tumor growth inhibition. Adapted from Abayasiriwardana *et al.,* 2025.

‍

AstraZeneca tested AZD5863, a CLDN18.2-targeting TCE with reduced CD3 affinity to limit cytokine release, using the genO-panhCD3 model. This molecule is now in clinical trials.

Graph of tumor volume over time showing dose‑dependent tumor growth inhibition with AZD5863 compared with isotype control, indicating reduced tumor growth at higher doses. — **Figure 2 –** Tumor growth inhibition of MC38 cells expressing CLDN18.2 implanted in genO-panhCD3 mice. Mice were treated with different doses of AZD5863. Treatment with the TCE leads to efficient tumor growth inhibition. Adapted from Gaspar *et al.*, 2025.

‍

Our hCD3 mouse model portfolio includes options for testing trispecific TCEs, TCEs used in combination with immune checkpoint inhibitors, and TCEs featuring various Fc-engineered regions:

‍

Application	Model
Efficacy of bispecific or trispecific antibodies targeting hCD3 and/or hCD28, or of combination therapies	genO-panhCD3 genO-hCD3ε genO-hCD28 genO-panhCD3/hCD28 genO-panhCD3/hCD137 (4-1BB) genO-panhCD3/hPD-1 genO-panhCD3/hPD-1/hPD-L1
Efficacy of Fc-mediated T-cell engagers	genO-panhCD3/hFcγR

‍

Additionally, if you’d like to know more about our model portfolio for TCE assessment, you can find more information here.

‍

‍

hCD28 models:

genOway’s hCD28 models (genO-hCD28 and genO-panhCD3/hCD28) allow the evaluation of next‑generation TCEs that rely on CD28 co-stimulation. They display:

Physiological regulation and expression pattern of hCD28
Expression of different hCD28 isoforms

The genO-hCD28 model was validated by Sensei Biotherapeutics, among others, who characterized a tumor-selective bispecific antibody that conditionally co-stimulates T cells via CD28 in a pH- and VISTA-dependent manner:

‍

Graph of tumor volume over time showing strongest tumor growth inhibition with anti‑mPD‑1 combined with CD28xVISTA, compared with isotype control or single treatments, with significance indicated. — **Figure 3 –** Tumor growth inhibition of MC38 cells expressing VISTA implanted in genO-hCD28 mice. Mice were treated with CD28xVISTA pH sensitive alone or in combination with a murine anti-PD-1. Combination treatment of the TCE awith mPD-1 leads to efficient tumor growth inhibition. Adapted from Thisted *et al.*, 2025.

‍

‍

Cell Line portfolio:

genOway’s catalog of syngeneic cell lines expressing human TAAs or different human immune checkpoints increases the translatability of efficacy studies by ensuring:

Co-expression of both TCE targets
Direct testing of the clinical TCE (no surrogate required)
More realistic human target engagement in vivo

‍

Genetic background	Mouse model	Compatible cell lines
C57BL/6	genO-panhCD3 genO-hCD28 genO-hCD3ε genO-panhCD3/hCD28 genO-panhCD3/hCD137 (4-1BB) genO-panhCD3/hPD-1 genO-panhCD3/hPD-1/hPD-L1	genO-EL4-hCD19-LZ genO-EL4-hCD20-LZ genO-MC38-hPD-L1-hHER2-LZ genO-MC38-mPd-l1KO-hPD-L1-hFAP-LZ genO-MC38-PD-L1-mPD-L1KO genO-MC38-hPD-L1-LZ-mPD-L1KO genO-MC38-PD-L1-LZ
BALB/c	genO-panhCD3	genO-CT26-hPD-L1 genO-CT26-hEpCAM-LZ

‍

Furthermore, these cell lines can be customized to your specific needs.

‍

‍

Human Immune System (HIS) mice

‍

The genO-BRGSF-HIS model is a CD34⁺ HSC reconstituted mouse with a functional human immune system. It captures key tumor microenvironment features thanks to:

Functional human myeloid and lymphoid compartments upon CD34⁺ HSC-reconstitution
Dynamic recruitment and activation profile of immune cells into the TME shaped by tumor cell type and burden
Presence of functional γδ T cells

‍

This model recapitulates the tumor-immune dynamics as described in Martin et al., 2025, enabling the translational assessment of TCE efficacy:

‍