Targeting Cancer with a Bi-functional Peptide: In Vitro and In Vivo Results

摘要: Background: Current therapies to treat cancer, although successful for some patients, have significant side- effects and a high number of patients disease that is either non-responsive or which develops resistance. Our goal was design small peptide possesses similar functions an antibody drug conjugate with regard targeting killing cancer cells, but overcomes size restrictions. Materials Methods: We designed novel cancer-specific killer created by fusion the toxic (KLAKLAK)2 recognition LTVSPWY. Results. This bi-functional showed toxicity breast prostate neuroblastoma cell lines. Only low non-cancer colon lung lymphoma lines observed. In vivo injections caused tumor growth retardation compared mice treated control peptides. The MDA-MB-435S tumors in increased survival 80% at day 100 after implantation, whereas all animals died 70. Previous reports moiety LTVSPWY targets tumor-associated antigen HER2. Here we found our new TP-Tox also excerts on HER2-negative Therefore, searched molecular target bi- specific using immunoprecipitation mass spectrometry. data suggest possible interaction RAS GTPase-activating protein binding 1 (G3BP1). Conclusion: 23 amino acids demonstrated its ability bind kill several vitro strongly increase bearing vivo. toxin could be used future warrants further pre- clinical exploration. Cancer among most common causes death Western world. treatment classically involves surgical removal tumor, chemotherapy, radiation therapy. Unfortunately, escape malignant cells from primary prior surgery, side-effects off-target actions drugs, non-responsiveness, development