Photoimmunotherapy of human uveal melanoma cells.
To examine whether tumor-reactive monoclonal antibodies can be used to enhance photodestruction of human uveal melanoma cells, we conjugated photosensitizer chlorin e6 monoethylenediamine monoamide (CMA) with a melanoma-reactive monoclonal antibody IG12 and evaluated the effectiveness of this immunoconjugate (IC) in the destruction of OCM431 human uveal melanoma cells in vitro. RPMI1846 melanoma cells do not react with IC and were used as non-target cells. For control, target and non-target cells were treated with IC or light alone. The effects of IC and free CMA in the destruction of melanoma cells were compared. Cell survival was assessed by a colorimetric assay using tetrazolium salt MTT. Target (OCM431) cells preincubated with IC and irradiated with 5-40 J cm-2 showed light dose-dependent decrease in cell survival. At 40 J cm-2, OCM431 cells preincubated with IC showed only 6 +/- 1.4% viability. Under same treatment, non-target (RPMI1846) cells showed much less phototoxicity; cell survival was 54 +/- 2.1%. Treatment with free CMA and light at 40 J cm-2 showed similar phototoxicity to both target and non-target cells, with cell survival being 24.3 +/- 3.5% and 23.7 +/- 1.5%, respectively. These results show that our IC is effective in causing photodestruction of human uveal melanoma cells in vitro. The phototoxicity is selective and more potent than free CMA.
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.
L K
LK
Hu
T
T
Hasan
E S
ES
Gragoudas
L H
LH
Young
D000911:Antibodies, Monoclonal; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates