Anti-AXL antibodies, antibody fragments and their immunoconjugates and uses thereof

An antibody or antibody fragment that specifically binds to Axl protein, said antibody or antibody fragment comprising a heavy chain variable region including three complementarity determining regions having H1, H2, and H3 sequences, and a light chain variable region including three complementarity determining regions having L1, L2, and L3 sequences, wherein:

• (a) the H1 sequence is X1GX2X3MX4 (SEQ ID NO:
• 1);
• (b) the H2 sequence is LIKX5SNGGTX6YNQKFKG (SEQ ID NO:
• 2);
• and
• (c) the H3 sequence is GX7X8X9X10X11X12X13X14DYX15X16 (SEQ ID NO:
• 3),
• wherein
• X1 is T or A or W,
• X2 is H or A,
• X3 is T,
• X4 is N,
• X5 is P,
• X6 is S,
• X7 is H,
• X8 is Y,
• X9 is E,
• X10 is S,
• X11 is Y,
• X12 is E,
• X13 is A,
• X14 is M,
• X15 is W, and
• X16 is G, and
• (d) the L1 sequence is KASQDX17X18SX19VX20 (SEQ ID NO:
• 4);
• (e) the L2 sequence is X21X22X23TRX24T (SEQ ID NO:
• 5);
• and
• (f) the L3 sequence is QEX25X26SX27X28X29X30 (SEQ ID NO:
• 6),
• wherein
• X17 is V,
• X18 is S or V,
• X19 is A,
• X20 is A,
• X21 is W,
• X22 is Q,
• X23 is D,
• X24 is H,
• X25 is H,
• X26 is F,
• X27 is T or P,
• X28 is P,
• X29 is L, and
• X30 is T or R;
• wherein the isolated antibody or antibody fragment has a higher binding affinity to human Axl protein in a tumor microenvironment of pH 5.8 to 7.0 in comparison with a non-tumor microenvironment of pH 7.2 to 7.8;
• and
• the antibody or antibody fragment has a ratio of binding affinity to the human Axl protein in the tumor microenvironment to a binding affinity to the human Axl protein in the non-tumor microenvironment of at least 1.5:1.