Near-Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody.

Abstract

Prostate-specific membrane antigen (PSMA) is a membrane protein that is overexpressed manifold in prostate cancer and provides an attractive target for molecular therapy. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photoabsorber conjugate (APC). Here, we describe the efficacy of NIR-PIT, using a fully human IgG1 anti-PSMA monoclonal antibody (mAb), conjugated to the photoabsorber, IR700DX, in a PSMA-expressing PC3 prostate cancer cell line. Anti-PSMA-IR700 showed specific binding and cell-specific killing was observed after exposure of the cells to NIR light in vitro In the in vivo study, anti-PSMA-IR700 showed high tumor accumulation and high tumor-background ratio. Tumor-bearing mice were separated into 4 groups: (i) no treatment; (ii) 100 μg of anti-PSMA-IR700 i.v.; (iii) NIR light exposure; (iv) 100 μg of anti-PSMA-IR700 i.v., NIR light exposure was administered. These were performed every week for up to 3 weeks. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other control groups (P < 0.001), and significantly prolonged survival was achieved (P < 0.0001 vs. other control groups). More than two thirds of tumors were cured with NIR-PIT. In conclusion, the anti-PSMA antibody is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with the anti-PSMA-IR700 antibody is a promising candidate of the treatment of PSMA-expressing tumors and could be readily translated to humans.Implications: NIR-infrared photoimmunotherapy (NIR-PIT) using a fully human anti-PSMA-IR700 conjugate showed potential therapeutic effects against a PSMA-expressing prostate cancer that is readily translated to humans. Mol Cancer Res; 15(9); 1153-62. ©2017 AACR.

• Authors: Tadanobu Nagaya, Yuko Nakamura, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Peter L Choyke, Hisataka Kobayashi
• Journal: Molecular cancer research : MCR (Mol Cancer Res) Vol. 15 Issue 9 Pg. 1153-1162 (09 2017) ISSN: 1557-3125 [Electronic] United States
• PMID: 28588059 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Antigens, Surface
• FOLH1 protein, human
• Glutamate Carboxypeptidase II

Topics

• Animals
• Antigens, Surface (pharmacology, therapeutic use)
• Cell Line, Tumor
• Female
• Glutamate Carboxypeptidase II (pharmacology, therapeutic use)
• Humans
• Immunotherapy (methods)
• Male
• Mice
• Mice, Nude
• Phototherapy (methods)
• Prostatic Neoplasms (drug therapy, therapy)