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Updated: Dec 10, 2025
Author Spotlight: Advancing Protein Engineering – Harnessing Evolution Through PRANCE and Lab Automation
Published on: January 12, 2024
Using phage-assisted continuous evolution (PACE) to evolve human PD1
Xiaoxiao Ye1, Min Tu1, Mingxin Piao1
1Jilin Province Engineering Laboratory of Plant Genetic Improvement, College of Plant Science, Jilin University, 5333 Xi'an Road, Changchun, 130062, China; Basic Forestry and Proteomics Research Center, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
Abstract:
PD1/PDL1 pathway plays a critical role in cancer immune responses. The immune checkpoint inhibitors of PD1/PDL1 have been well explored and developed for immunotherapies of solid tumors. Recently, various monoclonal antibodies targeting the PD1/PDL1 pathway have emerged and achieved remarkable success in clinical trials. However, challenges with these monoclonal antibodies have appeared during cancer therapies, including predictors of response, patient selection, and innate resistance. Thus, a competitive antagonist of native PD1/PDL1, with smaller size and lower side-effect, is required for future cancer therapies. In this study, we utilized a protein evolution system of phage-assisted continuous evolution (PACE) to evolve PD1 continuously. Our results indicated that the newly evolved PD1 bound to PDL1 with higher affinity. The interactome analysis further suggested that these evolved PD1s exhibited higher specificity with PDL1. Therefore, these evolved PD1s may be applied as a new tool for tumor immunotherapy.
Insights
Researchers evolved PD1 (Programmed cell death protein 1) using PACE to create improved antagonists for cancer immunotherapy. These evolved PD1 variants show higher affinity and specificity for PDL1, offering potential for more effective tumor treatments.
Area of Science:
- Immunology
- Molecular Biology
- Biotechnology
Background:
- The PD1/PDL1 pathway is crucial for regulating cancer immune responses.
- Current PD1/PDL1 inhibitors, primarily monoclonal antibodies, show success but face challenges like response prediction and resistance.
- There is a need for novel PD1/PDL1 antagonists with improved characteristics for cancer therapy.
Purpose of the Study:
- To evolve PD1 variants with enhanced binding affinity and specificity for PDL1.
- To explore the potential of these evolved PD1s as novel tools for cancer immunotherapy.
Main Methods:
- Utilized phage-assisted continuous evolution (PACE) for protein evolution.
- Performed interactome analysis to assess specificity.
Main Results:
- Successfully evolved PD1 variants with significantly higher binding affinity to PDL1.
- Demonstrated increased specificity of the evolved PD1s for PDL1 through interactome analysis.
Conclusions:
- The evolved PD1 variants represent promising candidates for next-generation cancer immunotherapies.
- These engineered PD1 proteins could overcome limitations of current monoclonal antibody treatments.
