Tumoricidal Capacities of Macrophages Photodynamically Activated With Hematoporphyrin Derivative

Abstract

Four days after administration to mice of small amounts (30-600 ng/mouse) of hematoporphyrin derivative (HPD), peritoneal macrophages exhibited a greatly enhanced Fc-receptor mediated phagocytic capacity as assayed by ingestion activity of IgG-coated sheep erythrocytes. Much higher doses (greater than 3000 ng/mouse) did not have this effect. The peritoneal macrophages activated by administration of HPD have tumoricidal capacity for IgG-coated retinoblastoma cells. We then studied in vitro photodynamic activation of macrophages by white and red fluorescent light irradiation of mouse peritoneal cells (mixture of macrophages and B and T lymphocytes) in media containing very low concentrations of HPD. A short (5 s) white fluorescent light exposure (1Wm-2) of peritoneal cells in a medium containing 0.03 ng HPD/mL produced the maximal level of ingestion activity of macrophages. A 15 s red fluorescent light exposure (1Wm-2) of peritoneal cells in a medium containing 0.1 ng HPD/mL produced the maximal level of ingestion activity of macrophages. Thus, photodynamic activation of macrophages with white fluorescent light is more efficient than that with red fluorescent light. This can be explained by the fact that HPD has a large absorption peak at about 364 nm which extends into the visible range, and decreasingly smaller absorption bands at 500, 535, 570 and 630 nm. In vitro photodynamically activated macrophages showed efficient tumoricidal activity regardless of the type (white or red) of light used. These results suggest that a low level of HPD promotes therapeutic immunopotentiation.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer

“…By blocking this immunosuppressive effect, the DBPMAF therapy may have permitted a more pervasive tumour destruction by PDT (Korbelik, 1996). Since macrophage activation for phagocytosis and subsequent antigen presentation is the first step of the immune development process, the PDT-induced immunosuppression was suggested to be related to the impairment of macrophage activation by PDT (Yamamoto et al, 1992). The adjuvant administration of DBPMAF bypasses the decapitated macrophage activation cascade leading to reversal of the immunosuppressive state.…”

“…The values for the two groups are statistically different (P<0.025) Adjuvant activity of GcMAF combined with PDT The comparative evaluation of GcMAF used as the adjuvant to PDT instead of DBPMAF is shown in Figure 5. Although a signif- The effect of DBPMAF on PDT-induced immunosuppression Since the immunosuppressive effects of PDT on the cellular level were examined in our earlier studies (Yamamoto et al, , 1992, in this work we examined the immune status of the whole animal by using the standard DTH assay. The induction of immunosuppression by SCCVII tumour treatment with PDT alone, or combined with DBPMAF therapy, was examined.…”

“…There are indications that the tumoricidal activity of these activated inflammatory cells makes an essential contribution to the antitumour effect of PDT (Korbelik, 1996;. Increased macrophage activity was demonstrated after PDT in vitro and in vivo (Yamamoto et al, , 1992Krosl et al, 1995).…”

Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line

“…The effect of the addition of heat-inactivated DMBAinduced tumor-bearing hamster serum on macrophagedirected cytotoxicity with GcMAF in HCPC-1 cells was also studied, since it was reported that the tumoricidal activity of activated macrophages was markedly enhanced by the addition of tumor-bearing patient serum in the human retinoblastoma cell line W24 (6).…”

“…Administration of the Gc protein-derived MAF (GcMAF) that was generated enzymatically in vitro from the Gc protein in human serum, bypasses the impaired macrophage activation cascade and efficiently activates macrophages. Highly activated macrophages have been reported to have a tumoricidal potential (6)(7)(8)(9). Pilot studies have reported the efficacy of GcMAF-based immunotherapy of metastatic cancer in animal and humans (10)(11)(12)(13).…”