Immuno-oncology models and solutions

Preclinical assessment of immune‑based cancer therapies

Immuno‑oncology (IO) therapies rely on complex interactions between tumor cells, immune cell populations and the tumor microenvironment. genOway offers a broad portfolio of services in immuno‑oncology, designed to support drug discovery and preclinical development across multiple therapeutic approaches - from early proof‑of‑concept to translational studies. Selecting the right preclinical model is therefore critical to de‑risk development, demonstrate mechanism of action and guide clinical strategy. To do so, you need to identify your scientific objective, whether it is to understand the mode of action of your therapeutic, or to analyze its efficacy and safety.

1. Define which application you need to test

Across therapeutic approaches, genOway models can be used to support:

• Efficacy: tumor growth inhibition, tumor clearance, survival
• Safety: cytokine release, immune‑related adverse effects‍
• Pharmacokinetics / Pharmacodynamics (PK/PD): exposure–response relationships
• Biodistribution: target and immune cell engagement across tissues‍
• Mechanism of action: immune activation, cell depletion, immune infiltration

2. Choose the right immuno‑oncology model

Before selecting amodel, several key questions should be addressed:

• What is the therapeutic mechanism? (immune activation, immune depletion, immune redirection, checkpoint modulation, etc.)
• Which immune populations are involved? (T cells, NK cells, myeloid cells, macrophages…)
• Is target expression required on tumor cells, immune cells, or both?
• Is a functional immune system required? (immunocompetent Knockin vs human immune system mice)
• What level of translational relevance is needed? (mechanistic vs clinical‑like responses)
• Does your therapeutic display cross-reactivity between mice and humans?

genOway supports these decisions by combining genetically engineered mouse models, syngeneic and humanized systems, and engineered cell lines tailored to each IO strategy.

‍

Our immuno‑oncology solutions portfolio - organized by therapeutic approach

‍

1. T‑cell engagers and redirecting therapies

(e.g.BiTEs, bispecific antibodies)

T‑cell engagers (TCEs) are designed to redirect cytotoxic T cells towards tumour cells by simultaneously binding a tumour antigen and a T‑cell receptor. These therapies enable highly targeted tumour killing, independent of natural antigen presentation.

Applications supported for TCEs

• Efficacy: tumor growth inhibition, tumor regression
• Mechanism of action: T-cell activation, tumor infiltration
• Safety: cytokine release assessment
• PK/PD: exposure-response relationships of TCEs

genOway solutions

• Syngeneic mouse tumor models engrafted with cell lines engineered to express defined tumor antigens (genO-panhCD3, genO-hCD28, genO-panhCD3/hCD28, genO-panhCD3/CD137 (4-1BB), genO-panhCD3/hFcγR, among many others)
• Mice reconstituted with human CD34⁺ cells developing a human immune system, which enable the evaluation of human specific T cell engagers (genO-BRGSF-HIS)
• Immunodeficient mice engrafted with human PBMCs (genO‑BRGSF‑PBMC) for rapid proof‑of‑concept efficacy assessment
• Engineered tumor cell lines expressing tumor antigens for in vitro and in vivo studies

‍

2) Immune cell depletion therapies

(e.g.anti‑CD20, anti-CCR8, macrophage- or Treg-targeting)

‍Immune cell depletion therapies aim to eliminate or modulate specific immune populations that contribute to tumour progression or immune suppression. By targeting cells such as B cells, Tregs or tumour‑associated macrophages, these approaches help reshape the tumour microenvironment and restore anti‑tumour immunity.

Applications supported for cell depletion therapies

• Efficacy: target cell depletion, tumor growth inhibition
• Mechanism of action: immune remodeling, changes in tumor immune infiltrates
• Safety: immune system perturbation
• Biodistribution: Analysis of biodistribution of immune cells

genOway solutions

• Knockin mouse models expressing human immune targets for human specific antibodies (genO-hCCR8/hCCL1 or genO-panhCD3 for testing depleting TCEs)
• Mice with a human immune system (genO-BRGSF-HIS) enabling the study of tumor-associated macrophages, Tregs or myeloid populations
• Engineered immune or tumor cell lines expressing the relevant targets

‍

3) Immune checkpoint inhibitors

(e.g.PD‑1/PD‑L1, CTLA‑4, emerging checkpoints)

‍Immune checkpoint inhibitors (ICIs) work by releasing inhibitory pathways that restrain T‑cell activity, enabling a stronger anti‑tumour immune response. These therapies have transformed oncology but require robust models to assess response variability, resistance mechanisms and combination strategies.

Applications supported for ICIs

• Efficacy: target cell depletion, tumor growth inhibition, combination therapy
• Mechanism of action: immune remodeling, analysis of immune activation markers
• Safety: immune system perturbation, over activation/inhibition of the immune system
• Biodistribution: Analysis of biodistribution of immune checkpoints

genOway solutions

• Humanized checkpoint knock in mice enabling testing of human antibodies (genO-hPD-1, genO-hPD-1/hPD-L1, genO-hCTLA-4, genO-hOX40, among many others)
• Cell lines expressing the humanized checkpoint
• Mice with a human immune system enabling evaluation of your ICI therapy (genO-BRGSF-HIS)

‍

4) Cell‑based therapies

(e.g.CAR‑T, CAR‑NK, adoptive cell transfer)

‍Cell‑based therapies, such as CAR‑T or CAR‑NK cells, involve the administration of engineered immune cells designed to recognise and eliminate tumour cells. Their efficacy depends on cell persistence, expansion and tumour infiltration, making specialised preclinical models essential.

Applications supported for cell-based therapies

• Efficacy: tumor clearance
• Mechanism of action and biodistribution: immune cell expansion and persistence
• Safety: on target/off tumor effects

genOway solutions

• Immunodeficient mouse models for human cell engraftment (genO-BRGSF)
• HIS mice for more physiological immune interactions (genO-BRGSF-HIS)
• Engineered tumor cell lines for antigen specific targeting

5) Innate immunity and myeloid‑targeted therapies

(e.g.STING agonists, macrophage reprogramming, NK‑cell therapies)

‍Innate immunity‑targeted therapies focus on activating or reprogramming myeloid and innate immune cells within the tumor microenvironment. By engaging pathways such as STING or modulating macrophages and NK cells, these approaches aim to initiate or amplify anti‑tumour immune responses, often in combination with other IO therapies.

Applications supported for innate immunity and myeloid targeted therapies

• Efficacy: innate immune activation, tumor growth inhibition, synergy with adaptive immune responses
• Safety: disturbances in the immune system, cytokine release syndrome
• Mechanism of action: changes in tumor microenvironment and innate immune activation
• PK: measuring the half-life of myeloid-targeted therapeutics
• Biodistribution: Analysis of biodistribution of myeloid cells

genOway solutions

• Immunocompetent Knockin mouse models with intact myeloid and NK compartments (genO-hSTING, genO-hFcγR, genO-hCD47/hSIRPα, genO-hVISTA)
• Mice with a human immune system enabling evaluation of your therapy (genO-BRGSF-HIS)
• Engineered cell lines

6) Beyond models: A translational approach to immuno‑oncology

genOway goes beyond supplying models by supporting:

• Model selection strategy
• Custom model development
• Translational study design
• Proof of concept studies

Our goal is to help you select the most relevant model at each stage of your immuno-oncology program, reducing risk and accelerating development.