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Near-Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody.
- Source :
-
Molecular cancer research : MCR [Mol Cancer Res] 2017 Sep; Vol. 15 (9), pp. 1153-1162. Date of Electronic Publication: 2017 Jun 06. - Publication Year :
- 2017
-
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 IgG <subscript>1</subscript> 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 .<br /> (©2017 American Association for Cancer Research.)
- Subjects :
- Animals
Antigens, Surface pharmacology
Cell Line, Tumor
Female
Glutamate Carboxypeptidase II pharmacology
Humans
Male
Mice
Mice, Nude
Antigens, Surface therapeutic use
Glutamate Carboxypeptidase II therapeutic use
Immunotherapy methods
Phototherapy methods
Prostatic Neoplasms drug therapy
Prostatic Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3125
- Volume :
- 15
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Molecular cancer research : MCR
- Publication Type :
- Academic Journal
- Accession number :
- 28588059
- Full Text :
- https://doi.org/10.1158/1541-7786.MCR-17-0164