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10.1038/ncomms15090

http://scihub22266oqcxt.onion/10.1038/ncomms15090
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C5436137!5436137!28489072
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suck abstract from ncbi


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pmid28489072      Nat+Commun 2017 ; 8 (ä): ä
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  • Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration #MMPMID28489072
  • Shin SM; Choi DK; Jung K; Bae J; Kim Js; Park Sw; Song KH; Kim YS
  • Nat Commun 2017[]; 8 (ä): ä PMID28489072show ga
  • Oncogenic Ras mutants, frequently detected in human cancers, are high-priority anticancer drug targets. However, direct inhibition of oncogenic Ras mutants with small molecules has been extremely challenging. Here we report the development of a human IgG1 format antibody, RT11, which internalizes into the cytosol of living cells and selectively binds to the activated GTP-bound form of various oncogenic Ras mutants to block the interactions with effector proteins, thereby suppressing downstream signalling and exerting anti-proliferative effects in a variety of tumour cells harbouring oncogenic Ras mutants. When systemically administered, an RT11 variant with an additional tumour-associated integrin binding moiety for tumour tissue targeting significantly inhibits the in vivo growth of oncogenic Ras-mutated tumour xenografts in mice, but not wild-type Ras-harbouring tumours. Our results demonstrate the feasibility of developing therapeutic antibodies for direct targeting of cytosolic proteins that are inaccessible using current antibody technology.
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