Potentiation of photodynamic therapy-elicited antitumor response by localized treatment with granulocyte-macrophage colony-stimulating factor.
Murine squamous cell carcinoma (SCCVII) cells were genetically engineered to produce marine granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF immunotherapy, based on the peritumoral injection of lethally irradiated GM-CSF-producing SCCVII cells, was examined as adjuvant to photodynamic therapy (PDT) treatment of this tumor. The GM-CSF immunotherapy administered three times in 48-h intervals, starting 2 days before the light treatment, substantially improved the curative effect of Photofrin-mediated PDT. A comparable effect of GM-CSF immunotherapy was observed in the combination with benzoporphyrin derivative-mediated PDT. The tumor-localized GM-CSF immunotherapy alone had no obvious effect on the growth of parental SCCVII tumors. This treatment did not significantly alter the differential peripheral WBC count and appeared not to affect tumor leukocyte infiltration. However, GM-CSF treatment did increase the cytotoxic activity of tumor-associated macrophages against SCCVII tumor cells. It appears, therefore, that tumor-localized immune stimulation by GM-CSF amplifies a PDT-induced antitumor immune reaction, which has a potentiating effect on tumor control.
Krosl
G
G
Cancer Imaging, British Columbia Cancer Agency, Canada.
Korbelik
M
M
Krosl
J
J
Dougherty
G J
GJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D017324:Hematoporphyrin Derivative / Q000008:administration & dosage; D007111:Immunity, Cellular; D007167:Immunotherapy; D007958:Leukocyte Count; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy / Q000379:methods*; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D017324:Hematoporphyrin Derivative; D016178:Granulocyte-Macrophage Colony-Stimulating Factor