Merocyanine 540-sensitized photoinactivation of high-grade non-Hodgkin's lymphoma cells: potential application in autologous BMT.
This paper reports on the preclinical evaluation of merocyanine 540 (MC540) as an agent for the inactivation of tumour cells in BM grafts from non-Hodgkin's lymphoma (NHL) patients. The three cell lines used for this study, OCI-LY13.1, OCI-LY13.2 and OCI-LY9, originate from two patients with high-grade NHL. The OCI-LY13.1 and OCI-LY13.2 lines are derived from the same patient. The OCI-LY13.1 line was established at the time of diagnosis while the OCI-LY13.2 line was established after the tumour had become refractory to therapy. When used under conditions that are known to preserve about 50% of normal human pluripotent hematopoietic progenitor cells (CFU-GEMM), MC540-sensitized photoirradiation reduced in vitro clonogenic OCI-LY9 cells by 4 orders of magnitude and OCI-LY13.1 and OCI-LY13.2 cells by > or = 5. Survival curves for OCI-LY13.1 and OCI-LY13.2 cells were similar and followed first order kinetics, while those for OCI-LY9 cells were distinctly biphasic. Suspension cultures established with photoinactivated lymphoma cells confirmed that MC540-sensitized photoirradiation was cytotoxic and capable of eliminating > or = 4 log of tumour cells. These results encourage the further exploration of MC540-sensitized photoirradiation as a means to purge autologous marrow grafts from NHL patients.
Itoh
T
T
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Messner
H A
HA
Jamal
N
N
Tweeddale
M
M
Sieber
F
F
D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D006801:Humans; D008027:Light; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D017319:Photosensitizing Agents; D011744:Pyrimidinones; C003954:merocyanine dye