Humanized Mouse Models – Enabling Translational Immuno-Oncology

Immuno-oncology (IO) drug development demands preclinical models that accurately reflect the human immune system’s interaction with tumors. LIDE’s humanized platforms provide flexible, high-fidelity solutions for evaluating checkpoint inhibitors, bispecific antibodies, CAR-T/NK therapies, ADCs, oncolytic viruses, and more, bridging the gap between discovery and clinical translation.

FeatureBenefits to Drug R&D
Human Immune ReconstitutionEnables evaluation of human-specific IO agents not cross-reactive with murine targets
Tumor–Immune InteractionsStudy T-cell infiltration, exhaustion, activation, and immunosuppressive mechanisms
Predictive of Clinical OutcomesCapture variability in immune response across donors and tumor types
Flexible Model TypesChoose from PBMC-reconstituted, CD34+ HSC models, or immune cell co-inoculation systems depending on your research goal

1. HuPBMC-Reconstituted Models

How it works

NCG mice engrafted with patient-derived xenografts (PDX) or cell line xenografts (CDX) are reconstituted via i.v. or i.p. injection of human PBMCs.

Applications
  • Evaluate human T-cell–targeted therapies (anti–PD-1, PD-L1, CTLA-4 antibodies, bispecifics)
  • Compare responses in PD-L1–high vs. PD-L1–low tumors
  • Study primary and acquired resistance to checkpoint blockade
Advantages at LIDE
  • Proprietary PBMC donor selection methods to optimize engraftment and response consistency
  • 30+ PD(L)1 antibody–resistant PDX models available with detailed clinical annotations

2. Co-Inoculation Platforms (HuPBMC + Tumor Cells)

How it works

Human immune cells (PBMCs, macrophages, dendritic cells) are pre-mixed with tumor cells before subcutaneous implantation.

Advantages
  • Immediate tumor–immune engagement from Day 0
  • Delayed GvHD issues as seen in classical reconstituted models
  • Highly flexible design for testing innate/adaptive modulators, bispecifics, and ADCs
  • Rapid readouts for target validation or MoA studies

3. CD34+ HSC Humanized Models

How it works

NCG mice receive hematopoietic stem cells, enabling multi-lineage human immune system reconstitution (T, B, NK, myeloid cells).

Applications
  • Long-term IO studies requiring sustained immune function
  • Evaluation of agents engaging both adaptive and innate immunity
  • Combination therapy testing over extended periods

4. Innate Immune Cell–Involved Models

LIDE is one of the few CROs to offer several co-transfer systems in its IO models:

  • M2 Macrophage Models: Model immunosuppressive TME; test macrophage-repolarizing agents (e.g., CD47, CSF1R inhibitors)
  • DC-Involved Models: Assess DC activators (e.g., CD40 agonists) alone or in combination with checkpoint inhibitors
  • Oncolytic Virus–Enabled Models: Evaluate oncolytic virotherapies in human immune–reconstituted mice to measure both direct tumor lysis and immune-mediated antitumor effects.

5. IO-FIVE®: Mini-PDX® for IO drugs

IO-FIVE™ (Immuno-Oncology Fast In Vivo Efficacy) is LIDE’s advanced adaptation of our proven MiniPDX® platform, purpose-built for immuno-oncology drug candidates. Using fresh patient tumor samples and humanized immune-reconstituted mice, IO-FIVE™ delivers actionable in vivo efficacy data for IO agents in as little as 14 days.

Learn more about IO-FIVE®
Choosing the Right IO Model
Model TypeProsCons
Murine Syngeneic Models· Fully immunocompetent mouse host
· Fast tumor growth and high take rate
· Ideal for early proof-of-concept IO studies
· Cost-effective and scalable		· Murine immune system differs from human
· Human-specific IO agents not always cross-reactive
· Limited predictive value for certain targets
Humanized Syngeneic Models· Combine syngeneic tumor speed with human target validation
· Useful for testing human-specific antibodies (e.g., PD-1, PD-L1 knock-in)
· Maintains intact immune interactions		· Requires genetically modified mice
· Target-specific scope; not a full human immune system
· Higher cost than standard syngeneic
CD34+ HSC Humanized Models· Long-term, multi-lineage immune reconstitution (T, B, NK, myeloid)
· No GvHD issues
· Suitable for chronic treatment studies and combination regimens		· Longer lead time to establish (3–4 months)
· Higher cost
· Potential variability in engraftment rates
HuPBMC-Reconstituted Models· Rapid establishment (2–3 weeks)
· Strong human T-cell activity
· Suitable for short-term IO efficacy studies
· Good for PD-1/PD-L1 and T-cell–engaging bispecifics		· Limited study duration (risk of GVHD)
· Donor-to-donor variability in immune reconstitution
· Primarily models adaptive immunity
HuPBMC + Tumor Co-Inoculation Models· Immediate tumor–immune interaction from Day 0
· No or Delayed GvHD issues
· Flexible design for testing innate/adaptive modulators
· Fast readouts for target validation and MoA studies		· Requires custom model setup
· Can be costlier than reconstituted models
Demonstrated IO Targets / Pathways available at LIDE
Target / PathwayTarget / Pathway
PD-1 / PD-L1 / CTLA-4LAG-3 / TIGIT / TIM-3
TGF-β / PD-L1PVRIG
GITRCSF1R
DLL3 / CD3CD47 / SIRPα
Claudin18.2 / CD3 / 4-1BBCD40
CD73 / CD39B7-H3-ADC / CD3
IL-2 / IL-15 / IL-12 BsAb or ProbodyEGFR-ADC / CD3
CD19 / CD20 / CD3GPRC5D / CD3
LILRB1 / LILRB2GPC3 BsAb
Ly6g6d BsAb(More in progress)

Watch our Director of IO rewview some of the novel humanized models available at LIDE

The breadth of LIDE’s IO platform supports studies for both adaptive and innate immunity, with standard reconstituted mouse models or unique co-inoculation models with CDX or PDX tissue.