Melanogenesis cascade as the molecular target for the development of chemo-thermo-immunotherapy : rationale and clinical application

Abstract

The biological property unique to melanoma cells resides in the biogenesis of melanin pigment (melanogenesis) within the specific compartments, melanosomes. This study showed that melanogenesis can be exploited to develop the tyrosinase-targeted drug delivery system (DDS) and chemo-thermo-immunotherapy (CTI therapy) for melanoma patients. It was concluded a) that NPrCAP/M can develop a novel DDS and anti-melanoma chemotherapy targeted to melanogenesis ; b) that NPrCAP/M with alternating magnetic field (AMF) to C57 BL mice with B16 melanoma inhibited the growth of re-challenged melanoma cells inoculated on to the opposite side of the body after the removal of the initially inoculated melanoma in mice ; c) that NPrCAP/PEG/M with AMF provided thermal heat which resulted in melanoma necrosis and immune reactions generating cytotoxic T cells and regressed distant skin metastases in human clinical trials and d) that novel chemo-thermo-immunotherapy with NPrCAP/PEG/M can, therefore, be developed for melanoma patients by exploiting the melanogenesis cascade.[Skin Cancer (Japan) 2009 ; 24 : 174-180]