Potentiation of the anti-tumour effects of Photofrin-based photodynamic therapy by localized treatment with G-CSF

Br J Cancer. 2000 Apr;82(8):1485-91. doi: 10.1054/bjoc.1999.1078.

Abstract

Photofrin-based photodynamic therapy (PDT) has recently been approved for palliative and curative purposes in cancer patients. It has been demonstrated that neutrophils are indispensable for its anti-tumour effectiveness. We decided to evaluate the extent of the anti-tumour effectiveness of PDT combined with administration of granulocyte colony-stimulating factor (G-CSF) as well as the influence of Photofrin and G-CSF on the myelopoiesis and functional activity of neutrophils in mice. An intensive treatment with G-CSF significantly potentiated anti-tumour effectiveness of Photofrin-based PDT resulting in a reduction of tumour growth and prolongation of the survival time of mice bearing two different tumours: colon-26 and Lewis lung carcinoma. Moreover, 33% of C-26-bearing mice were completely cured of their tumours after combined therapy and developed a specific and long-lasting immunity. The tumours treated with both agents contained more infiltrating neutrophils and apoptotic cells then tumours treated with either G-CSF or PDT only. Importantly, simultaneous administration of Photofrin and G-CSF stimulated bone marrow and spleen myelopoiesis that resulted in an increased number of neutrophils demonstrating functional characteristics of activation. Potentiated anti-tumour effects of Photofrin-based PDT combined with G-CSF observed in two murine tumour models suggest that clinical trials using this tumour therapy protocol would be worth pursuing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Animals
  • Bone Marrow Cells / pathology
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Colony-Forming Units Assay
  • Combined Modality Therapy
  • Dihematoporphyrin Ether / therapeutic use*
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Photochemotherapy*
  • Recombinant Proteins
  • Spleen / pathology

Substances

  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Dihematoporphyrin Ether
  • Filgrastim