Potentiation of the anti-tumour effects of Photofrin-based photodynamic therapy by localized treatment with G-CSF.
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.
Gołab
J
J
Department of Immunology, Institute of Biostructure, Warsaw, Poland.
Wilczyński
G
G
Zagozdzon
R
R
Stokłosa
T
T
Dabrowska
A
A
Rybczyńska
J
J
Wasik
M
M
Machaj
E
E
Ołda
T
T
Kozar
K
K
Kamiński
R
R
Giermasz
A
A
Czajka
A
A
Lasek
W
W
Feleszko
W
W
Jakóbisiak
M
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003114:Colony-Forming Units Assay; D003131:Combined Modality Therapy; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use*; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010778:Photochemotherapy; D011994:Recombinant Proteins; D013154:Spleen / Q000473:pathology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D017323:Dihematoporphyrin Ether; D000069585:Filgrastim