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Drug Development Expertise Empowering Research Services for Biologics

Efficacy Studies

Validated Efficacy Models for Oncology, Immunology & Metabolism

Establishing a rational design for in vivo efficacy study requires validated mechanisms of action (MOA) and qualified models for translational lead screening. At WuXi Biologics, our in vivo efficacy services focus on lead screening and dosage optimization, utilizing comprehensive oncology models such as syngeneic and CDX/PBMC models, specializing in bispecific T-cell engager (TCE) and antibody-drug conjugate (ADC) efficacy studies. For autoimmune & metabolic diseases, we have developed over 30 validated models, covering a wide range of clinical symptoms. These efficacy models are continuously updated to incorporate cutting-edge humanized platforms, offering tailored solutions to meet custom preclinical studies.

 

Key Features of Efficacy Services:

  • Diverse oncology (syngeneic, CDX/PBMC, IVIS/Orthotropic) and autoimmune & metabolic disease models
  • Rational design for potent donor screening, T cell infiltration, and IHC-validated target validation
  • Tailored to meet preclinical needs with expert support for troubleshooting and data interpretation

In vivo efficacy study for evaluation of treatment performance across validated tumor models, autoimmune, and metabolic diseases.

Efficacy Service Details:

Service Item

Description

Turnaround Time

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Efficacy Study

Sample requirements:

1. Protein amount: BW (mouse/25 g) × animal numbers × 150%

2. Protein purity: >98%

3. Endotoxin level: <2 EU/mg

4. Protein concentration (mg/mL): > dosing level (mg/kg)/10 (mL/kg)

 

Deliverables:

1. Tumor growth inhibition (TGI%) or index of disease symptoms

2. Body weight and clinical observations

3. IHC results for T cell infiltration or target validation

6-10 weeks

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Autoimmune & Metabolic Diseases

6-10 weeks

Explore Our Efficacy Models

Case Study #1: Tumor Growth Inhibition Study Using CDX/PBMC Model for Bispecific T-Cell Engagers (TCEs)

Case study showing tumor growth reduction in a CDX/PBMC model post TCE treatment for preclinical efficacy evaluation.

Figure A: We rationally selected a tumor model based on IHC target validation using prescreened donor to ensure reliable efficacy within a consistent therapeutic window. This CDX/PBMC model demonstrated high resolution with decent efficacy in tumor growth inhibition for bispecific TCE characterization.

Case Study #2: In Vivo Efficacy Studies Using Dextran Sulfate Sodium (DSS)-Induced Colitis Model

This case study evaluates the efficacy of an antibody treatment in the DSS-induced colitis model, a well-established preclinical model for inflammatory bowel disease (IBD).

Case study on evaluating the efficacy of an antibody treatment in a DSS-induced colitis model, a preclinical model for inflammatory bowel disease (IBD).

Figure 1: (A) Body weight changes and disease activity index (DAI) in DSS-treated mice demonstrated significant protection by the antibody treatment (blue) compared to the untreated control group (gray). (B) Histopathological analysis of colon tissues showed reduced inflammation and restored mucosal structure in the antibody-treated group, measured by H&E staining. Quantitative scoring of histological sections further confirmed a significant improvement in tissue morphology following treatment.

Case Study #3: Dulaglutide in Diet-induced obesity (DIO) model for Preclinical Efficacy Testing

This case study evaluates the anti-obesity efficacy of dulaglutide in a diet-induced obesity (DIO) model. The study monitored body weight changes, glucose tolerance, and fat mass reduction to assess the therapeutic impact of dulaglutide on metabolic dysfunction in obese mice.

Case study on evaluating the anti-obesity efficacy of Dulaglutide in a diet-induced obesity (DIO) model, monitoring body weight, glucose tolerance, and fat mass reduction.

Figure 1: (A) Blood glucose levels over time showed significant improvement in glucose regulation in the dulaglutide-treated group (blue) compared to the vehicle control. (B) The treated group exhibited enhanced glucose tolerance, as evidenced by lower glucose levels during the glucose tolerance test. (C) Quantification confirmed a significant reduction in fat mass in the dulaglutide-treated group compared to controls. (D) Imaging data from an IVIS system further validated reduced fat accumulation in the treated group, correlating with improved metabolic outcomes.

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Frequently Asked Questions for Efficacy Studies

Q: How does graft-versus-host disease (GVHD) affect PBMC CDX studies?

A: GVHD can emerge in a tumor cell line-dependent manner and must be monitored closely. Some models may show GVHD-related effects within about two weeks, while others remain more stable for longer periods. Signs can include tumor shrinkage in control animals, fur color changes, and other clinical observations. Experience with multiple donors and tumor lines is important for selecting workable models.

Q: Does lowering CD3 binding to reduce CRS risk also reduce efficacy?

A: Reducing CD3-driven activity may help lower CRS risk, but it can also reduce antitumor efficacy because T cell activation is part of the intended mechanism of action. The goal is usually not to eliminate immune activation completely, but to tune it to a level that maintains efficacy with acceptable safety.

Q: When should tumor inoculation be done relative to PBMC reconstitution in CDX/PBMC studies?

A: It depends on the tumor growth characteristics. For faster-growing tumors, PBMC reconstitution may be done first, followed by tumor inoculation. For slower-growing tumors, tumor cells may be implanted before PBMC inoculation. The study design should be tailored to the biology of each tumor model.

Q: Is there a human CD45 threshold for deciding whether a PBMC-reconstituted CDX model is suitable?

A: Human CD45 is dynamic after PBMC reconstitution, however around 5% human CD45 at approximately two weeks post-reconstitution is generally considered sufficient for a PBMC CDX model. At later time points, this percentage may rise further, often reaching 10% or higher.

Q: Can CDX/PBMC models be used to assess cytokine release syndrome (CRS)?

A: They can be used to evaluate CRS-related signals, but their translational value is limited because they do not represent a fully competent human immune system. In CDX/PBMC models, only part of the immune compartment is reconstituted, so nonhuman primate studies are generally considered more robust for assessing CRS risk.

Q: When should CDX/PBMC models be used instead of syngeneic or humanized mouse models for T cell engager efficacy studies?

A: CDX/PBMC models are often preferred for T cell engager efficacy studies because they are generally more robust, offering broader tumor cell line options, and incorporate human tumor cells with human donor-derived PBMCs for a more translational readout. Humanized mouse models can also be useful, but they often require more time, validation, and higher cost, especially when additional target humanization is needed.

Q: We have a bispecific antibody where one arm does not cross-react with the mouse antigen, but the other does. How can we evaluate this molecule in animal models?

A: We can use a humanized mouse model in which the non-cross-reactive target is replaced with its human counterpart. This allows us to evaluate both arms of the bispecific antibody.

Q: What inflammation models do you offer for in vivo studies (e.g., arthritis, asthma, IBD)?

A: We support a range of inflammation models including arthritis, asthma, SLE, IBD, dermatitis, and LPS-induced inflammation. We also utilize knock-in humanized models where relevant targets are humanized to support autoimmune disease research.

Q: Are you using CD34+ humanized mice in TCE studies?

A: Yes, we actively use CD34+ humanized mice for both autoimmune diseases and solid tumor models. We also have experience using these models for PK/PD evaluations of TCEs.

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