Extensive Efficacy Model Collections
29 Autoimmune Disease Modes
15 Syngeneic Models
87 CDX (PBMC) Models
27 IVIS Imaging Models
7 Metabolism Models
Immunology & Metabolism
Oncology
*Build engineered cell-lines and establish new models on demand
Comprehensive Immunohistology Capabilities
• Comprehensive panel of staining methods: Includes HE, IHC, IF, EHC, and TCR • In-depth tissue analysis: Target evaluation, antibody distribution, immune cells infiltration, and more • Qualified pathology analysis
T Cell Infiltration
Tumor Antigen IHC for Model Characterization & Selection
HE Staining
PBS
mAb1
mAb2
Relative Quantification
***
***
50
Lung Lung
40
High expression High expression
Medium expression Medium expression
Low expression Low Expression
Kidney
30
Multiplex IF for Immuno-Profiling
20
10
0
PBS
mAb1
mAb2
DAPI
hCD4
hCD8
Merged
Case Study 1: Single-Source Solution for In Vivo Characterization of TCE
In this case study, the PK of TCEs was evaluated in vivo . The dose-concentration-response relationship for efficacy was also determined using a cell-derived xenograft (CDX) and peripheral blood mononuclear cells (PBMC) model designed based on tumor target validation through immunohistochemistry (IHC).
Customized PK Platform for TCE
CDX/PBMC Efficacy Model for TCE NCI-H524 in NDG-hPBMC
Biotin
TCE-1 Fc+Fc TCE-1 CD3+Fc
1000
PBS B (0.54 mg/kg) B (0.18 mg/kg) B (0.06 mg/kg) A (0.36 mg/kg) A (0.12 mg/kg) A (0.04 mg/kg) W (0.45 mg/kg) W (0.15 mg/kg) W (0.05 mg/kg)
1000 1500 2000 2500
100
Fc-Fc
Target validation
10
• Customized PK platform: Enables precise measurement of total IgG and TCE levels • Validated CD3 antigen: Ensures specificity and efficacy • Rationally designed CDX and PBMC efficacy model: Supported by target validation to enable potent PBMC donor screening Case Study 2: Established hFcRn Mouse Model for Early-Stage Fc Engineering Assessment 0 7 14 1 Time (Day) CD3-Fc 0 7 14 0 500 Days aer treatment
21
In this case study, we use a well-established hFcRn mouse model to assess Fc engineering at an early stage and simulate the in vivo PK profiles of both human mice and non-human primates (NHPs). • Enhanced PK profiles: An Fc-engineered antibody shows improved PK compared to its wild-type counterpart. • Strong linear correlation in t1/2: A consistent t1/2 correlation was observed between hFcRn and NHP models.
PK Curve of hFcRn Mice IV Infusion
Linear Simulation of t 1/2 Between hFcRn Mice and NHP
5 10 15 20 25
Pearson’s r = 0.91; P < 0.001
1000
G1_Wt t1/2=113 G2-Fc Engineered t1/2=260h
100
10
1
5
10
15
20
25
0.1
hFcRn mice half life (days)
0
7
14
21
Time (Day)
Valente et al; mAbs; 2020, VOL. 12, NO. 1, 13
About WuXi Biologics
WuXi Biologics is a leading contract research, development, and manufacturing organization (CRDMO) that provides end-to-end capabilities to healthcare organizations worldwide. With operations in China, the United States, Ireland, Germany, and Singapore, we enable our partners to effectively and efficiently bring biologics and vaccines to patients worldwide through our comprehensive and high-quality drug development model.
The world’s leading global single-source platform from concept to commercialization
wuxibiologics.com | PS_BD@wuxibiologics.com
12-3-2024
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