Science subjournal: tumor specific antibody targeted inhibition of Ras mutant tumors

February 20, 2020 / Biogen / -- oncogenic Ras mutant (rasmut) protein is unable to be contacted and targeted by conventional antibodies due to its position in the cell, so it is impossible to target this mutation and treat cancer through conventional antibody program Picture source; Science advanced recently came from South Korea Asian University, chengjunguan University and orum therapeutics In cooperation with researchers from Inc, an IgG antibody targeting pan RAS, inras37, was reported The antibody can be specifically internalized into the cytoplasm of tumor cells and directly act on various rasmut subtypes activated in cells, blocking their interaction with effector proteins, thus inhibiting their downstream signal transduction Injecting inras37 into mice with small rasmut xenograft tumor by systemic administration can produce strong antitumor activity, but this antibody has little effect on the downstream rasmut tumor with simultaneous PI3K mutation, which can be overcome by combining PI3K inhibitor The researchers found that the Yap1 protein in rasmut dependent colorectal tumors can be up-regulated and lead to drug resistance under the induction of inras37, so inras37 combined with Yap1 inhibitor has synergistic antitumor effect in vivo and in vitro All in all, this study provides a promising antibody targeting Ras mutant tumor and corresponding treatment strategy, breaking the phenomenon that the antibody can not target this mutation Reference materials: Yong Sung Kim et al Direct targeting of oncogenic Ras mutants with a tumor specific cytosol pentrating antibility investments Ras mutant driven tumor growth Science advances 15 Jan 2020: Vol 6, No 3, eaay2174 doi: 10.1126/sciadv.aay2174