Near-infrared photoimmunotherapy targeting prostate cancer with Prostate-Specific Membrane Antigen (PSMA) antibody

Tadanobu Nagaya, Yuko Nakamura, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Peter L. Choyke, Hisataka Kobayashi

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

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 fullyhuman 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. Tumorbearing mice were separated into 4 groups: (i) no treatment; (ii) 100 mg of anti-PSMA-IR700 i.v.; (iii) NIR light exposure; (iv) 100 mg of anti-PSMA-IR700 i.v., NIR light exposure was administered. Thesewere performed every week for up to 3weeks. 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.

Original languageEnglish
Pages (from-to)1153-1162
Number of pages10
JournalMolecular Cancer Research
Volume15
Issue number9
DOIs
Publication statusPublished - Sep 1 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research

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