Abstract

Blockage of PD-1 proteins by immune checkpoint inhibitors showed accepted therapeutic effect in cancer But tumor microenvironment exerts their anti-tumor effect by various mechanisms Malignant cells have the ability of PD-1 PD-L1 protein oversynthesis which can be a defense action against immune checkpoint inhibitors and immunotherapy Binding nivolumab with platinum containing STAT1 will be used for reduction of PD-1 genetic level Nivolumab has the option of endocytosis while STAT1 is the transcription factor that binds to the DNA specifically PD-1 gene STAT1 is the activated protein in response to multiple cytokines stimulation of cancer cells which are the same for increasing PD-1 PD-L1 upregulation The used STAT1 in our therapeutic strategy is the activated form and loaded with platinum particles for damaging DNA bases in PD-1 promoter regions upon translocation to the nucleus STAT1-platinum molecule is connected to nivolumab Fc region by solamargine polymer for selective cancer cell targeting