Method for inhibiting intracellular activated RAS using intact immunoglobulin-type antibody having cytosol-penetrating ability and use thereof

An anti-RAS antibody,

• wherein the antibody comprises a heavy chain variable region (VH) that binds specifically to RAS-GTP comprising:
• a VH CDR1, VH CDR2 and VH CDR3, respectively comprising the amino acid sequences selected from the group consisting of:
• VHCDR1 SEQ ID NO:
• 11, VHCDR2 SEQ ID NO:
• 12, and VHCDR3 SEQ ID NO:
• 13;
• VHCDR1 SEQ ID NO:
• 14, VHCDR2 SEQ ID NO:
• 15, and VHCDR3 SEQ ID NO:
• 16;
• VHCDR1 SEQ ID NO:
• 17, VHCDR2 SEQ ID NO:
• 18, and VHCDR3 SEQ ID NO:
• 19;
• VHCDR1 SEQ ID NO:
• 20, VHCDR2 SEQ ID NO:
• 21, and VHCDR3 SEQ ID NO:
• 22;
• VHCDR1 SEQ ID NO:
• 23, VHCDR2 SEQ ID NO:
• 24, and VHCDR3 SEQ ID NO:
• 25;
• and
• VHCDR1 SEQ ID NO:
• 26, VHCDR2 SEQ ID NO:
• 27, and VHCDR3 SEQ ID NO:
• 28;
• and
• a light-chain variable region (VL) that penetrates the cell membrane comprising:
• a VL CDR1, VL CDR2, and VL CDR3, respectively comprising the amino acid sequences selected from the group consisting of:
• VLCDR1 SEQ ID NO:
• 32, VLCDR2 SEQ ID NO:
• 33, VHCDR3 SEQ ID NO:
• 34;
• and
• VLCDR1 SEQ ID NO:
• 32, VLCDR2 SEQ ID NO:
• 33, VHCDR3 SEQ ID NO:
• 40;
• wherein 2nd and 4th amino acids starting from the N-terminus of the light-chain variable region are respectively substituted with leucine (L) and methionine (M), (wherein the positions of the amino acids are numbered according to the Kabat numbering system).