An anti-PSMA bivalent immunotoxin exhibits specificity and efficacy for prostate cancer imaging and therapy

Adv Healthc Mater. 2013 May;2(5):736-44. doi: 10.1002/adhm.201200254. Epub 2012 Nov 22.

Abstract

Prostate specific membrane antigen (PSMA) is overexpressed on prostate tumor cells and the neovascular endothelia various solid tumors. A bivalent immunotoxin generated by fusing a fold-back single-chain diabody derived from the Fv fragments of an anti-PSMA monoclonal antibody with a truncated diphtheria toxin (DT) containing the activity and translocation domains [A-dmDT390-scfbDb(PSMA)] might be suitable for targeted therapy of tumors that overexpress PSMA. In this study, a PSMA-positive and a PSMA-negative prostate cancer cell lines were treated with immunotoxin A-dmDT390-scfbDb(PSMA) in order to study the tumor targeting specificity and therapeutic potential of the immunotoxin. The cellular uptake and selective toxicity of the immunotoxin were evident in monolayer cultures of PSMA-positive LNCaP prostate cancer cells but not in cultures of PSMA-negative PC-3 prostate cancer cells. Cellular accumulation of A-dmDT390-scfbDb(PSMA) increased with increasing incubation times and concentrations in LNCaP cells. The proportion of apoptotic LNCaP cells increased upon incubation with increasing doses of the fold-back immunotoxin. Optical imaging and MRI with the Alexa Fluor 680-labeled A-dmDT390-scfbDb(PSMA) confirmed the specific targeting and therapeutic efficacy of this immunotoxin towards PSMA-positive LNCaP solid tumor xenografts in athymic nude mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line, Tumor
  • Fluorescent Dyes
  • Humans
  • Immunotoxins / immunology*
  • Immunotoxins / therapeutic use*
  • Male
  • Microscopy, Fluorescence / methods*
  • Prostate-Specific Antigen / antagonists & inhibitors*
  • Prostate-Specific Antigen / immunology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology

Substances

  • Fluorescent Dyes
  • Immunotoxins
  • Prostate-Specific Antigen