A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug
2002

Human Fusion Protein for Targeted Cancer Treatment

publication Evidence: moderate

Author Information

Author(s): de Graaf M, Boven E, Oosterhoff D, van der Meulen-Muileman I H, Huls G A, Gerritsen W R, Haisma H J, Pinedo H M

Primary Institution: Vrije Universiteit Medical Centre

Hypothesis

Can a fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein selectively activate a non-toxic prodrug at tumor sites?

Conclusion

The C28-GUSh fusion protein can effectively convert a non-toxic prodrug into a toxic drug specifically at the tumor site.

Supporting Evidence

  • The fusion protein retained antibody specificity and enzyme activity.
  • It was able to convert a non-toxic prodrug to doxorubicin, resulting in cytotoxicity.
  • A bystander effect was demonstrated, showing that doxorubicin was detected in all cells when only a fraction expressed the fusion protein.

Takeaway

Scientists created a special protein that can help turn a harmless medicine into a powerful cancer-fighting drug right where the tumor is, without hurting other parts of the body.

Methodology

The study involved constructing a fusion protein and testing its ability to activate a prodrug in cancer cells.

Limitations

The prodrug activation may not occur uniformly throughout the tumor tissue.

Digital Object Identifier (DOI)

10.1038/sj.bjc.6600143

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