Targeting cancer cells by using an antireceptor antibody-photosensitizer fusion protein.
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.
Serebrovskaya
Ekaterina O
EO
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya, Moscow, Russia.
Edelweiss
Eveline F
EF
Stremovskiy
Oleg A
OA
Lukyanov
Konstantin A
KA
Chudakov
Dmitry M
DM
Deyev
Sergey M
SM
D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000276:immunology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007128:Immunoglobulin Fragments; D017319:Photosensitizing Agents; D011993:Recombinant Fusion Proteins