Photoimmunotherapy of hepatocellular carcinoma-targeting Glypican-3 combined with nanosized albumin-bound paclitaxel.
OBJECTIVE
Effectiveness of Glypican-3 (GPC3)-targeted photoimmunotherapy (PIT) combined with the nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for hepatocellular carcinoma was evaluated.


METHODS
GPC3 expressing A431/G1 cells were incubated with a phthalocyanine-derivative, IRDye700DX (IR700), conjugated to an anti-GPC3 antibody, IR700-YP7 and exposed to near-infrared light. Therapeutic experiments combining GPC3-targeted PIT with nab-paclitaxel were performed in A431/G1 tumor-bearing mice.


RESULTS
IR700-YP7 bound to A431/G1 cells and induced rapid target-specific necrotic cell death by near-infrared light exposure in vitro. IR700-YP7 accumulated in A431/G1 tumors. Tumor growth was inhibited by PIT compared with nontreated control. Additionally, PIT dramatically increased nab-paclitaxel delivery and enhanced the therapeutic effect.


CONCLUSIONS
PIT targeting GPC3 combined with nab-paclitaxel is a promising method for treating hepatocellular carcinoma.
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Building 10, Room B3B69, MSC1088, Bethesda, MD 20892, USA.
Hirofumi
H
Hanaoka
Takahito
T
Nakajima
Kazuhide
K
Sato
Rira
R
Watanabe
Yen
Y
Phung
Wei
W
Gao
Toshiko
T
Harada
Insook
I
Kim
Chang H
CH
Paik
Peter L
PL
Choyke
Mitchell
M
Ho
Hisataka
H
Kobayashi
D000418:Albumins / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D053673:Glypicans / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000627:therapeutic use*; D010789:Phototherapy / Q000379:methods
C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; C105937:GPC3 protein, human; D053673:Glypicans; D017239:Paclitaxel
Glypican-3; hepatoma; monoclonal antibody; nab-paxlitaxel; nanodelivery; photocyanine dye; photoimmunotherapy