Inhibitory effects of merocyanine 540-mediated photodynamic therapy on cellular immune functions: A role in the prophylaxis of graft-versus-host disease?

• Extracorporeal PDT with MC540 inactivates a broad range of lymphocyte functions.
• MC540-PDT does not prevent GVHD in most murine models of allogeneic transplantation.
• MC540-PDT may prevent GVHD in transplant regimens that encourage mixed chimerism.

Merocyanine 540-mediated photodynamic therapy (MC540-PDT) has been used in clinical trials for the purging of autologous hematopoietic stem cell grafts. When the same combinations of dye and light were applied to human peripheral blood lymphocytes, a broad range of T- and B-cell functions were impaired, prompting speculations about a potential role of MC540-PDT in the prophylaxis of graft-versus-host disease (GVHD). We here report on the effects of MC540-PDT on in vitro functions of murine lymphocytes as well as a preliminary evaluation of MC540-PDT for the prevention of GVHD in murine models of allogeneic bone marrow transplantation. Mixed lymphocyte reactions, proliferative responses to lectins, interleukin-2 and lipopolysaccharide, T-cell-mediated lysis, and NK activity were all inhibited by moderate doses of MC540-PDT. Whether MC540-PDT reduced the incidence and/or the severity of GVHD in murine models of allogeneic hematopoietic stem cell transplantation depended on the composition of the mismatched grafts and the intensity of the preparative regimen. MC540-PDT was only beneficial (i.e. reduced the incidence and/or severity of GVHD) when the spleen cell content of grafts was low and/or the radiation dose of the preparative regimen was not myeloablative, and, therefore, may have encouraged mixed chimerism.

Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation. It is caused by donor lymphocytes that recognize recipient cells as foreign and attack them. As we report here, extracorporeal PDT with merocyanine 540 (MC540) inhibits a broad range of lymphocyte functions while preserving enough hematopoietic stem cells to ensure hematopoietic reconstitution after marrow ablative therapy. This raises the question if extracorporeal MC540-PDT of histo-incompatible grafts can reduce the incidence and/or severity of GVHD in allogeneic transplantation.Figure optionsDownload as PowerPoint slide