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

Ekaterina O. Serebrovskaya, Eveline F. Edelweiss, Oleg A. Stremovskiy, Konstantin A. Lukyanov, Dmitry M. Chudakov, Sergey M. Deyev

Research output: Contribution to journalArticle

102 Citations (Scopus)

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 immuno-photosensitizer, consisting of a specific anti-p185HER-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 p185HER-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.

Original languageEnglish
Pages (from-to)9221-9225
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number23
DOIs
Publication statusPublished - 9 Jun 2009
Externally publishedYes

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Photosensitizing Agents
Antibodies
Neoplasms
Proteins
Light
Immunoglobulin Fragments
Photochemotherapy
Recombinant Proteins
Antineoplastic Agents
Cisplatin
Antigens

Keywords

  • KillerRed
  • Phototoxicity
  • Reactive oxygen species

ASJC Scopus subject areas

  • General

Cite this

Targeting cancer cells by using an antireceptor antibody-photosensitizer fusion protein. / Serebrovskaya, Ekaterina O.; Edelweiss, Eveline F.; Stremovskiy, Oleg A.; Lukyanov, Konstantin A.; Chudakov, Dmitry M.; Deyev, Sergey M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 23, 09.06.2009, p. 9221-9225.

Research output: Contribution to journalArticle

Serebrovskaya, Ekaterina O. ; Edelweiss, Eveline F. ; Stremovskiy, Oleg A. ; Lukyanov, Konstantin A. ; Chudakov, Dmitry M. ; Deyev, Sergey M. / Targeting cancer cells by using an antireceptor antibody-photosensitizer fusion protein. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 23. pp. 9221-9225.
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