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

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.

SUBMITTER: Serebrovskaya EO 

PROVIDER: S-EPMC2695119 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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

Serebrovskaya Ekaterina O EO   Edelweiss Eveline F EF   Stremovskiy Oleg A OA   Lukyanov Konstantin A KA   Chudakov Dmitry M DM   Deyev Sergey M SM  

Proceedings of the National Academy of Sciences of the United States of America 20090520 23

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 p  ...[more]

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