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 language | English |
|---|---|
| Pages (from-to) | 9221-9225 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 106 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - 9 Jun 2009 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Targeting cancer cells by using an antireceptor antibody-photosensitizer fusion protein
AU - Serebrovskaya, Ekaterina O.
AU - Edelweiss, Eveline F.
AU - Stremovskiy, Oleg A.
AU - Lukyanov, Konstantin A.
AU - Chudakov, Dmitry M.
AU - Deyev, Sergey M.
PY - 2009/6/9
Y1 - 2009/6/9
N2 - 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.
AB - 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.
KW - KillerRed
KW - Phototoxicity
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=67249146583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67249146583&partnerID=8YFLogxK
U2 - 10.1073/pnas.0904140106
DO - 10.1073/pnas.0904140106
M3 - Article
VL - 106
SP - 9221
EP - 9225
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 23
ER -