Targeted sonodynamic therapy of cancer using a photosensitizer conjugated with antibody against carcinoembryonic antigen.
The goal of this study was to develop a strategy for the selective destruction of cancer cells by ultrasonic irradiation in the presence of an antibody-conjugated photosensitizer. To this end, a photoimmunoconjugate (PIC) was prepared between ATX-70, a photosensitizer of a gallium-porphyrin analogue, and F11-39, a high affinity monoclonal antibody (MAb) against carcinoembryonic antigen (CEA), which is often overexpressed in various carcinoma cells. This conjugate, designated F39/ATX-70, retained immunoreactivity against purified CEA and CEA-expressing cells as determined by enzyme-linked immunosorbent assay, flow cytometry and immunofluorescence microscopic analysis. The cytotoxicity of F39/ATX-70 against CEA-expressing human gastric carcinoma cells in vitro was found to be greater than that of ATX-70 when applied in combination with ultrasound irradiation. When in vivo anti-tumor effects in a mouse xenograft model were assessed, intravenous administration of F39/ATX-70 followed by ultrasonic irradiation produced a marked growth inhibition of tumor compared with irradiation alone or irradiation after administration of ATX-70. These results suggest that the PIC between anti-CEA MAb and ATX-70 may have applications in sonodynamic therapy where destruction of CEA-expressing tumor is required.
Abe
Hironori
H
Department of Biochemistry, Fukuoka University School of Medicine, Japan.
Kuroki
Motomu
M
Tachibana
Katsuro
K
Li
Tieli
T
Awasthi
Aradhana
A
Ueno
Aruto
A
Matsumoto
Hisanobu
H
Imakiire
Takayuki
T
Yamauchi
Yasushi
Y
Yamada
Hiromi
H
Ariyoshi
Asami
A
Kuroki
Masahide
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D000918:Antibody Specificity; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D018796:Immunoconjugates / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011166:Porphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014464:Ultrasonic Therapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D017319:Photosensitizing Agents; D011166:Porphyrins; C081908:ATX 70