Targeted photolysis of melanoma cells by Alfa-Terthienyl derivative labeled antimelanoma monoclonal antibody

摘要

Antibody targeted chemotherapy is a relatively new technique which involves the specifically carrier mediated delivery of chemotherapeutic agents to tumors or other pathogens for the treatment of such diseases. Conjugation of antibodies with photosensitizers (PSs) can also lead to potential therapeutic agents which combine photodynamic cytotoxicity with specific antibody binding. The antibody medicated delivery of a photosensitizer molecule and the target destruction upon irradiation by light followed by production of singlet oxygen or other radicals, results in a higher therapeutic ratio compared to the conventional photodynamic therapy (PDT). In this study the naturally occurring PS Alfa-Terthienile (ATT) was chemically derivatized with an amino group specific reactive side arm and in order to exploit its toxicity as an effector function suitable for targeted photolysis, covalently conjugated to the 225.28S monoclonal antibody (mAb) specific for the high molecular weight melanoma associated antigen (HMW-MAA). The 225-28S-ATT conjugate prepared was then tested against the melanoma cell line Colo38 in comparison with HT29 tumor cells, not recognized by 225-28S mAb, as negative control. The selective uptake of labeled mAb 225-28S-ATT and the melanoma cells death following irradiation an be observed. In conclusion the 225-28S-ATT conjugate, as far as one can judge from the effect on cells grown in vitro, seems a good candidate as a model to test the antibody targeted photolysis of melanoma cells for developing specific antimelanoma therapeutic agents.