Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen

Anticancer Res. 2024 Jun;44(6):2343-2348. doi: 10.21873/anticanres.17041.

Abstract

Background/aim: The standard treatment for localized prostate cancer involves surgical removal of the prostate with curative intent. However, when tumor cells persist in the operation site, there is high risk of local recurrence and tumor spread, leading to stressful follow-up treatments, impaired quality of life, and reduced overall survival. This study examined photoimmunotherapy (PIT) as a new treatment option for prostate cancer cells.

Materials and methods: We generated conjugates consisting of either a humanized antibody or Fab fragments thereof targeting the prostate specific membrane antigen (PSMA), along with our silicon phthalocyanine photosensitizer dye WB692-CB1. PSMA-expressing prostate cancer cells were incubated with the antibody dye or Fab dye conjugates and cell binding was measured using flow cytometry. Cells were irradiated with varying doses of red light for dye activation, and cytotoxicity was determined by erythrosin B staining and subsequent analysis using a Neubauer counting chamber.

Results: Specific cytotoxicity was induced with the antibody dye conjugate in the prostate cancer cells in a light dose-dependent manner. Treatment of the cells with the Fab dye conjugate resulted in lower cytotoxicity, which could be attributed to a reduced binding affinity and a reduced dye uptake of the Fab fragment.

Conclusion: Our new antibody dye and Fab dye conjugates offer potential for future intraoperative PIT in patients with localized prostate cancer, with the aim to ensure complete removal of tumor cells from the surgical area, to avoid local recurrence, and to improve clinical outcome.

Keywords: Fab fragment; Prostate cancer; antibody; photoimmunotherapy; prostate specific membrane antigen.

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, Surface* / immunology
  • Antigens, Surface* / metabolism
  • Cell Line, Tumor
  • Glutamate Carboxypeptidase II / immunology
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Immunoglobulin Fab Fragments* / chemistry
  • Immunoglobulin Fab Fragments* / immunology
  • Immunoglobulin Fab Fragments* / pharmacology
  • Immunotherapy* / methods
  • Male
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Phototherapy / methods
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / radiotherapy
  • Prostatic Neoplasms* / therapy

Substances

  • Immunoglobulin Fab Fragments
  • Antigens, Surface
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Photosensitizing Agents
  • Antibodies, Monoclonal, Humanized