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

Photofrin(TM)-based photodynamic therapy (PDT) has recently been approved f or palliative and curative purposes in cancer patients. It has been demonst rated 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-CS F) as well as the influence of Photofrin(R) and G-CSF on the myelopoiesis a nd functional activity of neutrophils in mice. An intensive treatment with G-CSF significantly potentiated anti-tumour effectiveness of Photofrin(R)-b ased PDT resulting in a reduction of tumour growth and prolongation of the survival time of mice bearing two different tumours: colon-26 and Lewis lun g carcinoma. Moreover, 33% of C-26-bearing mice were completely cured of th eir tumours after combined therapy and developed a specific and long-lastin g immunity. The tumours treated with both agents contained more infiltratin g neutrophils and apoptotic cells then tumours treated with either G-CSF or PDT only. Importantly, simultaneous administration of Photofrin(R) and G-C SF stimulated bone marrow and spleen myelopoiesis that resulted in an incre ased number of neutrophils demonstrating functional characteristics of acti vation. Potentiated anti-tumour effects of Photofrin(R)-based PDT combined with G-CSF observed in two murine tumour models suggest that clinical trial s using this tumour therapy protocol would be worth pursuing. (C) 2000 Canc er Research Campaign.