Antibody Humanization Services
Service Background
Antibody humanization technology was developed to improve the safety and efficacy of antibody therapeutics. Non-human antibodies, such as mouse, rabbit, or camelid nanobodies (VHH antibodies), can elicit immunogenic responses when used directly as therapeutic agents. Humanization technology significantly reduces this risk, enabling safer clinical application.
JWE applies Yeast Surface Display (YSD) at both the antibody discovery and humanization validation stages, allowing high-affinity candidate antibodies to be screened without animal experiments, followed by sequence optimization for humanization. The entire process is efficient, safe, and customizable.
Antibody Humanization Workflow
The general workflow for antibody humanization is as follows:
- Screen candidate antibody sequences using yeast display.
- Compare candidate sequences with human antibody germline gene databases to identify closely related VH/VL templates.
- Define antibody frameworks (FR) and CDR regions using IMGT, Kabat, and Chothia databases.
- Use CDR grafting to generate fully or partially humanized FR sequences.
- Introduce back mutations to maintain the affinity, stability, and solubility of the humanized antibody at levels comparable to the parental antibody.
Different antibody sources show significant differences in FR regions: VH humanization is mature for mouse and camelid antibodies, whereas rabbit antibodies require optimization of both VH and VL FR regions. JWE combines 3D structural modeling and extensive experience to establish rigorous humanization protocols, ensuring optimal antibody performance.
Service Content
| Step | Service Content | Deliverables | Timeline |
|---|---|---|---|
| Antibody Humanization Design |
- Antibody structure modeling - Determination of human antibody germline templates - CDR grafting and back mutation design - Design of 5 humanized antibody variants |
- Gene sequence information - At least 1 variant with affinity comparable to the parental antibody - Experimental report |
3-6 weeks |
| Candidate Antibody Expression | Gene synthesis and construction of mammalian expression vectors, small-scale expression validation | Small quantity expression samples | 1-2 weeks |
| Antibody Activity Validation |
- ELISA measurement of EC50 (with parental sequence control) - Affinity validation (BLI/SPR) - Optional FACS activity assay |
Validation data report | 2-3 weeks |
| Humanized Antibody Expression & Purification | Scale-up expression of candidate clones and affinity purification | Purified antibody samples | 2-3 weeks |
Service Advantages
- Simultaneous optimization of heavy and light chains ensures antibody integrity
- Humanization degree after modification >90%
- Humanized antibodies maintain affinity comparable to parental antibodies
- Applicable for multi-species antibodies, including mouse, rabbit, and camelid nanobodies (VHH)
- Full process using Yeast Surface Display for efficient candidate screening
- No animal experiments required; fast, safe, and customizable
