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Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9221-5. doi: 10.1073/pnas.0904140106. Epub 2009 May 20.

Targeting cancer cells by using an antireceptor antibody-photosensitizer fusion protein.

Author information

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya, Moscow, Russia.

Abstract

Antibody-photosensitizer chemical conjugates are used successfully to kill cancer cells in photodynamic therapy. However, chemical conjugation of photosensitizers presents several limitations, such as poor reproducibility, aggregation, and free photosensitizer impurities. Here, we report a fully genetically encoded immunophotosensitizer, consisting of a specific anti-p185(HER-2-ECD) antibody fragment 4D5scFv fused with the phototoxic fluorescent protein KillerRed. Both parts of the recombinant protein preserved their functional properties: high affinity to antigen and light activation of sensitizer. 4D5scFv-KillerRed showed fine targeting properties and efficiently killed p185(HER-2-ECD)-expressing cancer cells upon light irradiation. It also showed a remarkable additive effect with the commonly used antitumor agent cisplatin, further demonstrating the potential of the approach.

PMID:
19458251
PMCID:
PMC2695119
DOI:
10.1073/pnas.0904140106
[Indexed for MEDLINE]
Free PMC Article

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