Secreted and tumour targeted human carboxylesterase for activation of irinotecan
2002

Targeting Colon Cancer with a New Enzyme Therapy

publication Evidence: moderate

Author Information

Author(s): Oosterhoff D, Pinedo H M, van der Meulen I H, de Graaf M, Sone T, Kruyt F A, van Beusechem V W, Haisma H J, Gerritsen W R

Primary Institution: Vrije Universiteit Medical Center

Hypothesis

Extracellular conversion of the prodrug CPT-11 into its active form will enhance the bystander effect in treating colon cancer.

Conclusion

The study successfully constructed a secreted form of carboxylesterase that activates the prodrug CPT-11, leading to increased toxicity against colon cancer cells.

Supporting Evidence

  • Both secreted forms of carboxylesterase showed enzyme activity and effectively activated CPT-11.
  • The fusion protein C28-sCE2 specifically bound to EpCAM expressing colon cancer cells.
  • Incubation with the secreted enzymes and CPT-11 resulted in significant growth inhibition of colon cancer cells.

Takeaway

Scientists created a special enzyme that helps turn a cancer medicine into a stronger version that can kill more cancer cells. This could help treat colon cancer better.

Methodology

The study involved constructing and testing a secreted form of carboxylesterase and its fusion with a specific antibody to enhance drug activation in colon cancer cells.

Limitations

The study does not provide in vivo evidence to confirm the advantages of the targeted enzyme over the non-targeted version.

Digital Object Identifier (DOI)

10.1038/sj.bjc.6600519

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